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Background: There is little research of psychiatric comorbidity differences among people with different types of drug dependence in Chinese population. We explored demographic and comorbid psychiatric differences among methamphetamine-dependent males (MDs), heroin-dependent males (HDs) and methamphetamine and heroin co-dependent males (M/HDs) in Hunan province, China. Methods: A cross-sectional, structured and clinical interview method was used to examine differences in DSM-IV-TR Axis I Disorders among 346 MDs, 698 HDs and 247 M/HDs from three compulsory rehabilitation centers and two voluntary rehabilitation centers in Hunan. Results: MDs and M/HDs were younger, more likely to choose inhalation administration, less likely to have a family history of substance use, less likely to have undergone detoxification treatment, had higher incomes and shorter duration of drug use than HDs. Overall, methamphetamine-dependence related to higher rates of current and lifetime psychotic disorders, lifetime hallucinogen use disorders. Heroin-dependence related to higher rates of current and lifetime substance-induced mood disorders, sedative/hypnotic/anxiolytic and other drug use disorders and current alcohol use disorder. For M/HDs, they were more likely to have any other lifetime substance use disorders than MDs and HDs. Conclusions: There were substantial differences in epidemiological characteristics and comorbidity among MD, HD and M/HD groups, which highlights the urgent need to develop treatment services and policies for drug-specific users in China. [ABSTRACT FROM AUTHOR]