1) The study examined factors associated with major depressive disorder in a sample of 509 homosexually active gay-identified men who completed a survey at high HIV caseload general practices in Sydney and Adelaide, Australia. 2) Younger age, lower income, more daily life stressors, passive coping strategies, less social support, less involvement in the gay community, and more sexual problems were independently associated with a current diagnosis of major depressive disorder. 3) The results suggest that both social factors rather than HIV status alone are associated with major depression in this population, and that early social and structural interventions may help reduce isolation and mental health issues.