Chronic fatigue syndrome (CFS) is often preceded by a viral illness and has recurrent "flu-like" symptoms. We compared demographic, clinical, and laboratory features (markers of inflammation and viral infection) among 717 patients with chronic fatigue (CF) with and without a self-reported postinfectious onset to identify associated clinical and biologic findings and to examine the subset of patients with CFS. Only subjective fever, chills, sore throat, lymphadenopathy, poorer functional status, and attribution of illness to a physical condition were significantly associated with a postinfectious onset. The features of patients with CFS were virtually identical to those of the broader category of patients with CF. We conclude that a postinfectious onset was not associated with a pattern of abnormalities across multiple psychosocial and biologic parameters.