Except for the rare epsilon22 genotype it remains largely unsettled whether apolipoprotein E genotype influences an individual's referral to lipid clinics. To test this hypothesis, we compared genotype distributions among 156 hypercholesterolemic and 83 hypertriglyceridemic patients attending a lipid clinic with that among 9241 individuals sampled from the Danish general population. The relative genotype frequencies of epsilon22, epsilon32, epsilon42, epsilon33, epsilon43, and epsilon44 were 0.005, 0.126, 0.026, 0.564, 0.251, and 0.027 in the general population, which differed from genotype frequencies in both hypercholesterolemic (chi2: P = 0.01) and hypertriglyceridemic patients (chi2: P < 0.001). By comparison with epsilon33, epsilon44 predicted a 2-fold increase whereas epsilon32 predicted a 2-fold decrease in the attendance rate at the lipid clinic for hypercholesterolemic patients (95% confidence intervals: 1.1-4.3 and 0.2-0.9). Among hypertriglyceridemic patients, epsilon22, epsilon42, epsilon43, and epsilon44 versus epsilon33 predicted 13-, 3-, 1 1/2-, and 3-fold attendance rates at the lipid clinic, respectively (95% confidence intervals: 4.5-39.9, 1.2-8.4, 1.0-2.8, and 1.1-7.6). These findings are in accordance with the fact that epsilon44 raises cholesterol levels, epsilon32 reduces cholesterol levels, and epsilon22, epsilon42, epsilon43, and epsilon44 raise triglyceride levels in comparison with epsilon33. These data suggest that hypercholesterolemic individuals carrying epsilon44 and hypertriglyceridemic individuals carrying epsilon22, epsilon42, epsilon43, or epsilon44 are relatively more often referred to lipid clinics than carriers of epsilon33.