Forty-five psychiatric patients with chronic fatigue syndrome (CFS) were compared, using the case-control method, to two control groups selected from the same practice and matched on age, gender, and psychiatric diagnosis. The first control group (C-I, N=90) was selected on the basis of relatively good physical health. The second control group (C-II, N=45) was selected without regard to physical health. The reported family history of physical health revealed: the CFS mothers died at a younger age than the C-II mothers; both parents died before age 65 among the CFS parents more frequently than did the C-I parents; and the CFS parents had an increased prevalence of cancer, autoimmune disorders, and CFS-like conditions as compared to the families of one or both control groups. The reported family history of mental disorders revealed no significant differences in any of these conditions between the CFS patients and either control group.