Our objective was to measure serum angiotensin-converting enzyme (ACE) activity in patients with onchocerciasis. Serum ACE activity is commonly used in the diagnosis and follow-up of patients with sarcoidosis. However, serum ACE activity can also be elevated in a number of other granulomatous disorders. In onchocerciasis, a parasitic disease affecting millions of people in Africa and Central and South America, granulomatous tissue around adult worms has been identified, yet raised serum ACE activity has not been reported so far. We measured serum ACE activity in serum samples from 42 onchocerciasis patients and 39 endemic controls previously enrolled in two studies concerning the side effects after invermectin treatment in Sierra Leone, West Africa. The mean ACE activity in the patient group was 53.8 units/liter (S.D. 19.8) compared with 35.2 units/liter (S.D. 14.0) in the control group (p < 0.0001). Nine of 42 patients had elevated ACE activity (mean of the endemic controls +/- 2 S.D.) compared with 1 of 39 controls (p = 0.01). Sensitivity and specificity of elevated ACE in serum from onchocerciasis patients from Sierra Leone was 21 and 97%, respectively. ACE activity was not related to the microfilarial skin load or development of side effects after ivermectin treatment. Serum ACE activity can be elevated in onchocerciasis. Clinicians should be aware of this phenomenon when determining serum ACE activity in persons from endemic areas.