BACKGROUND: Gender differences in the relationship between alcohol use and depressive symptoms are inconsistent, and few studies have addressed this issue in Russia. Because this finding may have important implications for interventions to reduce alcohol misuse or alcohol related problems in Russia, we conducted a study to investigate whether the association between alcohol use and depressive symptoms differs by gender at high risk for HIV. METHODS: We used the Alcohol Use Disorders Identification Test (AUDIT) and the 10-item Center for Epidemiological Studies Depression Scale to measure alcohol use and depressive symptoms among 307 patients who attended a clinic for sexually transmitted infections in St. Petersburg, Russia. Logistic regression models were applied for the analysis. RESULTS: The comparison of data between men and women revealed a significant quadratic term of alcohol use and significant interactions between alcohol use and gender on depressive symptoms. Men with an AUDIT score in the first and fourth quartiles were more likely to report depressive symptoms in comparison to men in the second quartile. Their odds ratios (ORs) and 95% confidence intervals (CIs) were 7.54 (2.00-28.51) and 5.06 (1.31-19.63), respectively. Among women, a linear trend was observed such that those who misused alcohol were three times more likely to have depressive symptoms than those who did not misuse alcohol (OR = 3.03, 95% CI, 1.05-8.80). CONCLUSION: The association between alcohol use and depressive symptoms differed by gender. Additional research is needed to investigate this relationship in Russia. Strategies to reduce alcohol-related problems in Russia may need to consider these differences.