Angiotensin I-converting enzyme (ACE), which is synthesized by vascular endothelial cells, is sometimes elevated in diabetic subjects. To determine whether serum ACE is elevated in subjects at high risk of malignant microangiopathy, serum ACE activity in 34 normotensive, type 1 insulin-dependent diabetic subjects with persistent microalbuminuria (30-300 mg/24 h) was compared with that in 30 normotensive, normoalbuminuric type 1 diabetic subjects of the same age [37 +/- 15 (mean +/- SD) vs 38 +/- 14 years], sex (21 M/13 F vs 15 M/15 F), stage of retinopathy (14 vs 16 nil/11 vs 7 background/6 vs 4 preproliferative/3 vs 3 proliferative) and HbA1c (7.7 +/- 1.9 vs 8.2 +/- 1.0%). Serum ACE activity of diabetic subjects was also compared with 120 age and sex related healthy controls. Serum ACE activity was higher in subjects with microalbuminuria than in those with normoalbuminuria (406 +/- 114 vs 359 +/- 97 IU/l; P = 0.03), or in controls (307 +/- 95 IU/l; P = 0.0001). Normoalbuminuric subjects also had higher ACE activity than controls (P = 0.02). Serum ACE activity was not related to diabetes duration (r = 0.01; NS), HbA1c (r = 0.05; NS), or stage of retinopathy in diabetic subjects (r = 0.06; NS), while stage of retinopathy was related to age (r = 0.42; P = 0.003) and to diabetes duration (r = 0. 74; P = 0.0001) in these subjects. Elevated ACE activity occurs in type 1 diabetic subjects, especially in those with microalbuminuria. This may give early indication of lesions in vascular endothelial cells.