Background: The only large, registry-based twin study of depression using diagnostic criteria assessed by structured interview included only women. We present results from a comparable study of men. Methods: Data were collected using a standardized telephone interview of men from the Vietnam Era Twin Registry. Both twins from 3372 pairs participated. Proband-wise concordance rates and biometric modeling were used to analyze the data. Results: The diagnosis of major depression (MD), as defined by DSM-III-R, and the subtype of severe/psychotic MD were significantly affected by genetic (h2 = 0.36 and 0.39, respectively) and nonshared environmental (e2 = 0.64 and 0.61, respectively) factors but not by family environmental factors. Dysthymia and mild and moderate MD were affected by family environmental (c2=0.27, 0.08, and 0.14, respectively) and nonshared environmental (e2=0.73, 0.92, and 0.86, respectively) factors but not by genetic factors. Early-onset (before age 30 years) and late-onset (after age 30 years) MD were significantly affected by genetic (h2=0.47 and 0.10, respectively) and nonshared environmental (e2=0.53 and 0.90, respectively) factors. Early- onset MD was significantly more heritable than late-onset MD. Conclusions: The magnitude of genetic and environmental effects on depression in men is similar to that previously reported in women. Also similar to previous findings, more severe and earlier-onset depression may be more strongly affected by genetic factors, but differences in the reliability of reports of depression associated with severity may inflate estimates of the effect of the unique environment and deflate heritability estimates for less severe depression.