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Background: Alcohol and drug use continue to figure heavily in the experience of the contemporary homeless population. The comparison among pattern of use plays a central role in the cross-cultural view of this topic. This article shows the results of comparing the data concerning alcohol and other drug abuse and dependence among the homeless population of Madrid (Spain) and Los Angeles (USA)., Methods: Data come from two studies carried out independently in each city. Both studies used a comparable methodology which included the same inclusion and diagnostics criteria, representative sampling methods and similar diagnostic structured interviews. In the present study, the data from these two studies are combined in a unique database which allows global and item-to-item comparison between the two studies., Results: The results show different sociodemographic profiles for each city. Once controlled for the sociodemographic differences (age, education, current employment status and marital status), the life and 12-month prevalence rates of alcohol and other drug disorders (DSM-III-R) are also different. There are also significant differences in social, emotional and health problems associated with the consumption of alcohol and other drugs. The Madrid and LA samples also present differences in the time patterns of the beginning of the homelessness situation and the onset of alcohol- and drug-related disorders., Conclusions: The pattern of results is discussed in the light of the differences in both socioeconomic and cultural among Madrid and Los Angeles which might explain, in turn, differences in the homelessness situation as well as in the alcohol and other drug use patterns.