We report the clinical, laboratory, and pathological findings in a series of 52 consecutive patients with adult celiac sprue observed over a 20-year period. The frequency of that diagnosis increased from an average of 0.7 case/year during the period 1966-1975 to 5.8 cases/year during the period 1981-1985. Apart from two patients with dermatitis herpetiformis, nonclassical clinical presentations were observed in 16 of 50 (32%) patients overall and in 13 of 28 (46%) patients diagnosed since 1981. Diarrhea was the most common complaint leading to the diagnosis; since 1981, hematologic abnormalities warranted investigation in 38% of the patients. Decreased iron stores (88%), decreased red cell folate (82%), or both (74%), and abnormal radiographic studies of the small bowel (83%) were the most sensitive tests in the diagnostic investigation. We conclude that atypical or nonclassical presentations of adult celiac sprue, mostly with hematologic abnormalities, are not uncommon.