We determined the clinical efficacy of captopril for the prevention of new or stone growth in patients with homozygous cystinuria. Nine patients with a history of multiple cystine stones despite standard fluid and alkalization therapy received 50 mg. captopril, 3 times daily in addition to the standard therapy. Before treatment the rate of new stone formation or stone growth ranged from 0.7 to 2.0 events (mean 1.2) per patient-year for 1 to 3 years of observation (mean 1.9). During treatment the rate ranged from 0 to 3.0 events (mean 1.03) per patient-year for 0.5 to 6 years (mean 2.9). Although statistical significance was not evident for the group as a whole (p = 0.35), our findings suggest that captopril may be clinically efficacious in at least some patients with difficult to control cystinuria. Recommendations regarding its indications in this setting are made.