OBJECTIVE: Underlying cultural differences in the meaning of alcohol problems and dependence symptoms can lead people from different societies to systematically vary in their responses to a diagnostic interview, in ways that may be difficult for researchers to quantify or control. We identify four different ways that cultures can vary in their accounts of dependence symptoms, potentially leading to problems with the cross-cultural applicability of diagnostic criteria: (1) in terms of thresholds of symptom severity, or the point at which respondents from different societies recognize a symptom of dependence as something serious; (2) in the problematization of drinking-related states, or whether the symptoms described in official nomenclature on addiction even count as alcohol problems in all cultures; (3) in causal assumptions about how alcohol-related problems arise; and (4) in the extent to which there exist culture-specific manifestations of symptoms not adequately captured by official disease nomenclature. METHOD: Comparable data on the meaning of alcohol dependence criteria were collected from key informants in nine sites worldwide under the auspices of the WHO/NIH Cross-Cultural Applicability Research Project. Qualitative analysis compares and contrasts descriptions of ICD-10 dependence criteria across sites along the above four dimensions of cultural variation. RESULTS: While descriptions of dependence symptoms were quite similar among key informants from sites that share norms around drinking and drunkenness, they varied significantly in comparisons between sites with markedly different drinking cultures. Contrary to expectation, descriptions of physical dependence criteria appeared to vary across sites as much as the more subjective symptoms of psychological dependence. CONCLUSIONS: Problems with the cultural applicability of international nomenclature warrant careful consideration in future comparative research on addiction, although comparisons of dependence made across some cultural boundaries are likely to be much more problematic than comparisons made across others. Findings on dependence should be interpreted in light of what is known about the drinking cultures and norms of the societies involved. Future nosologies and diagnostic interview schedules should take into account a broad base of cultural experiences in conceptualizing alcohol dependence, in developing criteria and operationalizations and in determining the diagnostic significance of these.