Acid cholesteryl ester hydrolase activity of mononuclear leukocytes was measured in 52 Type 2 (non-insulin-dependent) diabetic patients. Enzyme activity was significantly lower in the diabetic patients than in 14 age-matched control subjects (0.89 +/- 0.08 (mean +/- S.E.) vs. 2.20 +/- 0.17 nmol/mg protein/hr, p less than 0.01). In diabetic patients undergoing diet treatment only, the enzyme activity was significantly lower in poorly controlled patients than in well controlled patients (0.43 +/- 0.03 vs. 1.15 +/- 0.24 nmol/mg protein/hr, p less than 0.01). In the diabetic patients, there was a significant negative correlation between the enzyme activity and serum total cholesterol or low density lipoprotein cholesterol level (r = -0.361, p less than 0.01, n = 52 or r = -0.630, p less than 0.01, n = 28). These results suggest that a low level of acid cholesteryl ester hydrolase activity in mononuclear leukocyte might play an important role in the progression of atherosclerosis in Type 2 diabetes.