Differences between patients with postinfectious chronic fatigue syndrome (CFS, n = 16) and noninfectious CFS (n = 20) were clarified. The noninfectious CFS group had problems in family and developmental history, and had chronic stresses. Members of the postinfectious CFS group were social extroverts while those in the noninfectious CFS group was neurotic and introspective. Natural killer cell activity was suppressed in both groups. These findings suggest that the postinfectious CFS group and the noninfectious CFS group differed in their pathogenesis until the onset of CFS. The latter group should be considered as a variant of psychiatric disorder and treated accordingly.