Apolipoprotein E (apoE) has an essential role in lipoprotein metabolism, but recent studies have also revealed other functions associated with it,eg, neurologic and malignant diseases. We studied the association between apoE phenotypes E2/3,E3/3,and E4/3 and blood pressure after adjustment for covariates, as well as the association between phenotypes and adjusted plasma glucose and insulin levels in the standard oral glucose tolerance test in a random middle-aged population-based cohort of 259 men and 267 women. Systolic blood pressure was associated with apoE phenotype in the men with moderate or heavy alcohol consumption (>115 g/week), the mean systolic blood pressure value being 16 mm Hg higher in the E2/3 and 11 mm Hg higher in the E3/3 phenotypes than in the E4/3 phenotype, P = .04. No association was seen in occasional drinkers or teetotalers (lowest tertile <24 g/week), whereas in the middle tertile the association was intermediate. The same association was seen with diastolic blood pressure. In men, there was a significant correlation between systolic blood pressure and alcohol consumption in the E2/3 phenotype (r(s) = 0.71, P < .01) and in the E3/3 phenotype (r(s) = 0.25, P < .01) but not in the E4/3 phenotype (r(s) = 0.03, NS). No association between apoE phenotypes and insulin resistance was observed. In conclusion, in middle-aged men, apoE phenotype significantly influences the blood-pressure-increasing effect of alcohol consumption. This gene-environment interaction may have marked implications for the prevention and treatment of hypertension. (C) 1998 American Journal of Hypertension, Ltd.