Our current understanding of parasite communities rests on several decades of fruitful studies of helminths (Noble, 1960; Schad, 1963; Kennedy, 1975; Scott and Gibbs, 1986; Stock and Holmes, 1988; Esch et al., 1990; Fernandez and Esch, 1991; Booth and Bundy, 1992; Kennedy and Bush, 1992). Many of the ecological and evolutionary insights from these pioneering studies could be tested among parasitic protists as well, building from analyses of relatively static, simple patterns among a few congeners toward those of dynamic interactions among multiple genera. Among helminths, for instance, Dobson (1985, 1990; Dobson and Roberts, 1994) has emphasized that aggregated intraspecific distributions may diminish interspecific competition, and Lotz and Font (1991, 1994; Lotz et al., 1995) have stressed that species rarity and recruitment may modulate patterns of interspecific association. Four species of Plasmodium cause human malaria, P. falciparum, P. malariae, P. ovale, and P. vivax. Sympatric combinations of these species occur in human populations and within infected individuals. Various phenomena associated with species co-occurrence have been studied as such for more than a century, e.g., Thayer and Hewetson (1895), since an era in which the very existence of more than one species was subject to debate. Biogeographic anomalies such as the absence of P. vivax and presence of P. ovale in West Africa and the spotty worldwide distribution of P. malariae have periodically attracted intense interest (see Molineaux, 1988), as have the frequencies of species co-occurrence within individuals and the possible correlates of mixed-species infections. This paper focusses on the latter 2 topics, particularly in those human populations in which recent reports suggest that only P. falciparum and 1 other Plasmodium species co-occur. In a massive survey of Plasmodium species prevalence in humans, Knowles and White (1930) recorded mixed-species infections at various frequencies at various sites on all 6 inhabited continents and noted that particular species combinations were often seasonal. They complained that mixed-species infections were often underreported, and demonstrated the phenomenon in a test of microscopists. Cohen’s (1973) analysis of the epidemiological literature concluded that deficits in the reported prevalence of mixed-species infections were not wholly artifactual, but common, often statistically significant phenomena with a previously unsuspected biological basis in heterologous immunity. His hypothesis was later extended to encompass the seasonal species patterns and surplus prevalence of mixed-species infections detected during the Garki project (Molineaux and Gramiccia, 1980; Molineaux et al., 1980). Richie’s analysis (1988) argued that species coexistence was made possible only through antigenic divergence and hence the avoidance of heterologous immunity. He suggested that competitive interspecific suppression in simultaneous infections might be balanced by some form of reciprocal successional facilitation. Unfortunately, few recent epidemiological reports examine mixed-species malaria infections; the studies by Fox and Strickland in Pakistan (1989) and Rosenberg et al. in Thailand (1990) are unique in reporting and discussing their findings that mixed P. falciparum–P. vivax infections occur at the levels expected and at levels far less than expected, respectively. The frequency with which unsuspected P. vivax infections emerge when protected patients clear their P. falciparum infections, in a variety of locations (Looareesuwan et al., 1987; Takagi et al., 1988; Nguyen and Keystone, 1989; Schuurkamp, 1992), hints that many mixed-species infections still escape detection. Though it is conceivable that this phenomenon derives solely from P. vivax hypnozoites, molecular-level detection methods produce wildly disproportionate increases in the reported prevalence of mixed-species infections (Barker et al., 1989; Relf et al., 1990; Brown et al., 1992; Arai et al., 1994) and may do so with several combinations of species; in studies comparing polymerase chain reaction (PCR) techniques to microscopy, for example, Snounou, Pinheiro et al. (1993) found that in Guinea Bissau mixed-species cases accounted for roughly half of a 142% increase and in Thailand (Snounou, Viriyakosol et al., 1993) three-quarters of a 22% increase in infections detected. Although P. ovale was seldom recognized as a distinct etiologic entity until the 1960s, reports of human populations in which just 1 or 2 Plasmodium species caused malaria became typical only as the global malaria-eradication campaigns of that era subsided. Accordingly, our predecessors based their analyses almost exclusively on studies in which 3 Plasmodium species were reported present. As we hypothesize that some conclusions about mixed-species Plasmodium infections may vary with the number or identity of the species involved, or both, we defer our examination of similar polysympatric circumstances and questions of heterologous immunity to a later paper. Here we address questions of spatial and temporal heterogeneity in the prevalence of dual infections. Cohen (1973) briefly examined geographic heterogeneity and seasonal variation in the contexts of “parasite rate,” i.e., overall prevalence, and “ecology,” respectively, and concluded that both factors (and both contexts) were at most minor influences. Richie (1988) considered both factors, at least implicitly, and concluded that no general relationships could obtain because “nearly every imaginable prevalence pattern has been found by one survey or another … there are geographic differences in the way in which human malaria species interact and … these interactions may even change from year to year in a given locale.” In this paper we analyze recent epidemiological data to determine if distinct prevalence patterns exist and, if so, if their influence is as weak as Cohen suggested and as confined to particular points in space and time as Richie proposed.