t haplotypes are a naturally occurring, autosomal, meiotic-drive system found on chromosome 17 of the house mouse. They show non-Mendelian transmission from heterozygous +/t males, such that 90% or more of the male's offspring inherit the t-bearing chromosome. Although they are expected to become rapidly fixed, surveys of natural populations typically report low overall frequencies of only ~15-25% +/t heterozygotes. Generally, such studies of t haplotypes in wild populations have sampled only small numbers of individuals due to the need to genotype mice by breeding, thus we have conducted a large survey of wild mice, Mus musculus domesticus, using DNA markers to examine the frequency and distribution of t haplotypes in natural populations. The overall frequency of +/t heterozygotes from our entire sample was 0.062, which is much lower than all previous estimates of t haplotype frequency. t haplotypes were patchily distributed and rare, and were present in only 46% of the populations we sampled. There were no significant sex-specific differences in the frequency of t haplotypes. Our data suggest that the frequency of +/t heterozygotes in independent populations varies with respect to population size and stability: t haplotypes were at low frequency in all large, relatively persistent populations, whereas they were at more variable, and often higher, frequencies in small, temporally unstable populations. The extinction and recolonization of many of the smaller populations may contribute to the greater variation in t haplotype frequency observed, and small populations may be important reservoirs of t haplotypes in the wild. The highest frequencies of t haplotypes were obtained from populations with semilethal, or complementing lethal, t haplotypes, where t/t homozygous mice were present., (© 1998 The Society for the Study of Evolution.)