Leucine 7 (Leu7) to proline 7 (Pro7) substitution in the neuropeptide Y (NPY) gene has been associated with higher serum total and low-density lipoprotein (LDL) cholesterol levels, particularly in obese subjects. We investigated the frequency of the Pro7 allele and the association of the polymorphism with serum lipid levels in patients with coronary heart disease (CHD). A total of 414 CHD patients (mean age 61 years, range 33-74) participated in the cross-sectional EUROASPIRE study. Of the subjects 39% used lipid-lowering drugs. The frequency of the Pro7 allele in CHD patients (0.082) did not differ from that in control subjects (0.071). The mean (+/-SD) serum total cholesterol concentration was higher in women with the Pro7 allele (7.57 +/- 0.57 mmol/L, n = 8) than in women with the Leu7Leu genotype (6.69 +/- 1.01 mmol/L, n = 69, P = 0.019), when subjects using lipid-lowering medication were excluded. In contrast, serum total cholesterol concentration did not significantly differ between the genotypes in men. The Leu7Pro polymorphism was not associated with serum LDL, high-density lipoprotein (HDL) cholesterol, and triglyceride concentrations. In conclusion, the Pro7 allele in the NPY gene was associated with higher serum total cholesterol concentration only in women with CHD who did not use lipid-lowering drugs.