The effect of alcohol on plasma high-density lipoprotein (HDL) cholesterol and on bile cholesterol saturation was measured in 12 healthy volunteers with a very low initial alcohol intake who drank 39 g alcohol daily for six weeks, and then abstained from alcohol for 6 weeks. HDL cholesterol (mean +/- SEM) rose significantly from 1.07 +/- 0.05 to 1.25 +/- 0.08 mmol/l (41.4 +/- 1.9 to 48.3 +/- 3.1 mg/dl) when alcohol was being consumed and fell to 1.04 +/- 0.06 mmol/l (40.2 +/- 2.3 mg/dl) during abstention. Bile cholesterol saturation index fell from 1.31 +/- 0.06 to 1.08 +/- 0.06 during the period of alcohol consumption and rose to 1.27 +/- 0.09 during abstention. There was a significant inverse correlation between bile saturation index and HDL cholesterol (r = -0.56). These data provide further evidence of a biochemical link between cardiovascular disease and cholesterol gallstones and suggest that moderate alcohol intake has some protective effect against both diseases.