Whereas serum lipoproteins have already been thoroughly studied in patients with premature atherosclerosis, cellular mechanisms for breaking down cholesterol esters have never been investigated in this population. We thus determined acid cholesterol esterase (ACE) activity in normal subjects and patients with coronary disease (CAD). This enzyme hydrolyzes intracellular esters. Results of this study show a lower ACE activity in patients with premature CAD. Furthermore, those CAD patients with very low ACE activities had fewer other risk factors for CAD than did those with higher ACE activities. This observation, taken with the lack of correlation between ACE and lipoprotein levels, suggests that ACE may be a separate risk factor, acting independently of serum lipoproteins in the genesis of premature CAD.