We report a patient with ulcerative colitis in whom agranulocytosis was diagnosed 5 wk after the initiation of sulfasalazine therapy. Concomitant features included fever and skin rash, and bone marrow examination revealed severe myeloid hypoplasia. Antineutrophil antibodies were absent from the serum. Recovery began during the 2nd wk and was characterized by a leukemoid reaction with thrombocytosis. Subsequently, the patient received 5-aminosalicylate enemas without adverse effects. Agranulocytosis, a rare effect of sulfasalazine, appears to occur almost invariably during the first 2 months of therapy, and prompt evaluation is therefore required in patients with unexplained fever or other nonspecific illness during this period.