Patients with persistent fatigue are often suspected of having psychiatric illnesses, particularly depression. The authors used the Diagnostic Interview Schedule to assess the lifetime prevalence of psychiatric disorders in 28 patients who met Centers for Disease Control case definition criteria for chronic fatigue syndrome. Compared with studies of the general population and studies of chronically medically ill patients who received the same structured interview, the rates of psychiatric illness in patients with the chronic fatigue syndrome appeared high. An examination of the medical histories of the 28 patients indicated that psychiatric disorders more often preceded the chronic fatigue than followed it.