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This article describes psychiatric and substance dependence comorbidities, lifetime rates of infectious disease, and reported high-risk sexual behaviors for methamphetamine-dependent, gay and bisexual men at entry to outpatient drug abuse treatment in Los Angeles. Participants' self-reports of high-risk sexual and drug use behaviors and of history of infectious disease status were correlated with diagnostic information from 155 Structured Clinical Interviews for the DSM-IV (SCID). A total of 82 participants met criteria for lifetime depressive disorders; 44 participants met criteria for lifetime anxiety disorders. Compared to those without psychiatric diagnoses, significant differences were observed in lifetime prevalence of sexually transmitted infections among those who have generalized anxiety disorder (higher rates of genital gonorrhea), specific phobia and major depressive disorder (higher rates of oral gonorrhea), social phobia (higher rates of syphilis) and bipolar disorder, type I (higher rates of HIV). Differences in infectious disease prevalence did not correspond to significantly different rates of high-risk sexual behaviors. Findings indicate that gay and bisexual men seeking outpatient treatment for methamphetamine dependence are likely to experience psychiatric comorbidity and to have high rates of infectious disease, including HIV, syphilis and gonorrhea.