The change of acid cholesteryl ester hydrolase activity in mononuclear leukocyte following treatment of diabetes mellitus was studied in 21 patients with non-insulin-dependent diabetes mellitus (NIDDM). Enzyme activity before treatment in the patients was significantly lower than that in 14 age-matched healthy subjects (1.20 +/- 0.15; mean +/- S.E. vs. 2.20 +/- 0.17 nmol/mg protein/h, P less than 0.01). Enzyme activity before treatment in the patients was significantly increased (P less than 0.05) after 4-8 weeks of treatment. However, enzyme activity of 1.43 +/- 0.14 nmol/mg protein/h observed after treatment in the patients was significantly lower (P less than 0.01) than that in the healthy subjects. There was a significant negative correlation between enzyme activity before treatment and the increase in enzyme activity following treatment (rs = -0.555, P less than 0.01, n = 21). These results indicate that low level of enzyme activity may be insufficiently improved by the treatment of diabetes, and the risk for the development of atherosclerosis as viewed from the enzyme activity may persist even after the treatment in NIDDM.