Relatively few studies have examined the personality characteristics of patients with chronic fatigue syndrome (CFS). The personality profiles of 38 CFS subjects were compared with 40 healthy controls and 40 subjects with multiple sclerosis (MS), a chronic illness that shares many symptoms with CFS (e.g., fatigue), but has a known neurological substrate. Subjects were examined within Cloninger's biosocial theory of personality, which delineates basic dimensions of temperament. Both illness groups displayed similarly elevated levels of Harm Avoidance, and lower levels of Reward Dependence as compared with healthy controls. The MS group showed a lower level of Persistence than controls and CFS subjects. Implications for the relationship between chronic illness and personality are discussed.