Background Data on the lifetime prevalence of psychiatric disorders in South Africa are of interest, not only for the purposes of developing evidence-based mental health policy, but also in view of South Africa's particular historical and demographic circumstances. Method A nationally representative household survey was conducted between 2002 and 2004 using the World Health Organization Composite International Diagnostic Interview (CIDI) to generate diagnoses. The data-set analysed included 4351 adult South Africans of all ethnic groups. Results Lifetime prevalence of DSM-IV/CIDI disorders was determined for anxiety disorders (15.8%), mood disorders (9.8%), substance use disorders (13.4%) and any disorder (30.3%). Lifetime prevalence of substance use disorders differed significantly across ethnic groups. Median age at onset was earlier for substance use disorders (21 years) than for anxiety disorders (32 years) or mood disorders (37 years). Conclusions In comparison with data from other countries, South Africa has a particularly high lifetime prevalence of substance use disorders. These disorders have an early age at onset, providing an important target for the planning of local mental health services.