Sarcoidosis may cause severe ventilatory impairment requiring corticosteroid treatment. Chloroquine (CQ) can be an effective treatment for lung sarcoidosis with few side effects, but has not been accepted as standard therapy. We investigated the benefits of prolonged CQ therapy in 23 symptomatic patients with biopsy-proven pulmonary sarcoidosis (duration, >/= 2 yr). Patients were initially treated for 6 mo with CQ, 750 mg/d, tapering every 2 mo to 250 mg/d. Eighteen patients were then randomized to either a Maintenance group (CQ, 250 mg/d) or to an Observation group (no CQ). After the initial treatment, significant improvement was observed in symptoms, pulmonary function, angiotensin-converting enzyme, and lung gallium scan. Patients randomized to the Maintenance group showed a slower decline in pulmonary function (FEV1, 51.4 +/- 28.2 ml/yr [Maintenance] versus 196.3 +/- 33.4 ml/yr [Observation], p < 0.02) and had fewer relapses: 2 of 10 patients in the Maintenance group at 29.5 +/- 4.9 mo versus 6 of 8 patients in the Observation group at 15.5 +/- 2.9 mo. Adverse effects were seen mainly during high-CQ dosage. We conclude that CQ should be an important consideration for the treatment and maintenance of chronic pulmonary sarcoidosis.