The relationship between the clinical course of sarcoidosis and serum angiotensin-converting enzyme (EC 3.4.15.1) activity was analyzed by observing 51 patients with sarcoidosis during a period of more than 1 yr. The patients were grouped into 3 categories irrespective of treatment: (1) sarcoid lesions in the chest disappeared within 1 yr, (2) sarcoid lesions remained for more than 1 yr with little improvement, (3) sarcoid lesions disappeared within 1 yr, but then relapsed. In group 1 (33 cases), the serum angiotensin-converting enzyme activity decreased from 35.9 +/- 2.0 to 22.0 +/- 1.3 nmol/ml/min after the chest roentgenogram cleared (P less than 0.005). In group 2 (12 cases), the mean serum angiotensin-converting enzyme activity after treatment was not significantly reduced, paralleling the lack of improvement. In group 3 (6 cases), a good correlation was observed between serum enzyme activity and clinical course. These findings indicate that serum angiotensin-converting enzyme activity is an indicator of the clinical course of sarcoidosis.