Neutropenia is a rare complication of procainamide therapy. However, over a period of 20 months, 8 patients developed severe neutropenia while taking a sustained-release preparation of the drug. Seven patients presented with fever and constitutional symptoms and one patient was asymptomatic. Bone marrow examinations showed myeloid aplasia or maturation arrest in 5 patients and myeloid hyperplasia in 1. Neutropenia resolved within 30 days of drug withdrawal, and all patients survived. A case-control study showed a significant association between sustained-release procainamide therapy and severe neutropenia in 5 of 114 patients (4.4%) recovering from open-heart surgery (Mantel-Haenszel chi square = 13.84; p less than 0.001). Thus, life-threatening neutropenia may be common with sustained-release procainamide preparations.