Serum angiotensin-converting enzyme (ACE) was measured in 150 insulin-dependent diabetes mellitus (IDDM) patients and 72 healthy subjects by radioassay, using [3H]-hippuryl-glycyl-glycine as a substrate. Mean (SD) serum ACE activity in diabetic patients was 120 +/- 33 nmol ml-1 min-1 (range 46-215) and was significantly increased by 56% compared to control values (77 +/- 23 nmol ml-1 min-1, range 46-125, P < 0.001). ACE activity > 125 nmol ml-1 min-1 was observed in 60 of 150 IDDM patients. 96 IDDM patients were normoalbuminuric (< 22 mg 24 h-1) and 49 patients were micro- or macroalbuminuric (range 22-6010 mg 24 h-1). Micro- and macroalbuminuric IDDM patients were found to have significantly greater ACE activity values than normoalbuminuric patients (128 +/- 36 vs. 115 +/- 30 nmol ml-1 min-1, P = 0.025). Metabolically well-controlled IDDM patients (glycosylated haemoglobin < or = 8%) had lower ACE activity values than the patients with glycosylated haemoglobin greater than 8% (109 +/- 20 vs. 127 +/- 32 nmol ml-1 min-1, P < 0.02). A significant correlation between degree of metabolic control and ACE activity was found (r = 0.435, P < 0.001) so that an increase in one glycosylated quartile unit is accompanied by an increase in ACE activity of 10.5 nmol ml-1 min-1. Thus ACE activity in the serum of IDDM patients was increased by 56% in 40% of the patients. It was increased in IDDM patients without complications and in patients with retinopathy or nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)