Our recent experiments demonstrated that squirrel monkeys fed ethanol (ETOH) at 12% of calories (Low ETOH) had significantly higher plasma lecithin: cholesterol acyltransferase (LCAT) activity than monkeys fed ETOH at 24% of calories (High Ethanol). Control animals had LCAT activity intermediate between that of Low and High ETOH primates. To test whether alcohol directly altered cholesterol esterification in vitro, LCAT activity was measured in pooled primate plasma incubated with ETOH at final concentrations of 60, 80, 160, and 240 mg/dl. A similar experiment was performed using incremental doses of ETOH's major metabolite, acetaldehyde. Peak cholesterol esterification occurred at 60 mg/dl which was comparable to plasma alcohol levels detected in Low ETOH monkeys (63 mg/dl) while LCAT activity was significantly depressed at 160 mg/dl which was similar to blood ETOH monitored in High ETOH primates (159 mg/dl). Maximum cholesterol esterification occurred at an acetaldehyde concentration of 0.45 mumoles/l. Our data indicate that ETOH can either stimulate or inhibit LCAT activity in vitro depending upon concentration and suggest that circulating blood alcohol may induce similar alterations in cholesterol esterification in vivo.