OBJECTIVE The aim of this study was to evaluate functional catechol-O-methyltransferase (COMT) genetic variation as a risk factor for eating disorders (ED). METHODS Eighty women receiving treatment for serious ED (52 for anorexia nervosa, 28 for bulimia nervosa) and 116 age-matched females in the control group underwent COMT genotyping for polymorphism in exon 4 (codon 158). Both the low-activity allele and the high-activity allele (H) were determined. RESULTS The H/H genotype was twice as frequent in the ED group as in the control group (52.5% in the ED group and 25% in controls, chi(2) = 15.5, d.f. = 2, p < 0.001, odds ratio = 3.343). The H/H genotype was found in 57.7% of anorexia nervosa patients (chi(2) = 16.860, p < 0.001, Hardy-Weinberg equilibrium = 0.003, odds ratio = 4.202). The H allele (val) was discovered in 66.9% of ED patients in comparison to 47.8% of patients from the control group (chi(2) = 13.89, p < 0.001, odds ratio = 6.088). In the anorexia group, H allele frequency was enhanced even higher (70.2 vs. 47.8%, chi(2) = 14.48, p < 0.001, odds ratio = 8.175). The genotype associations in the subgroup of bulimia patients were not significant, but a trend for a higher frequency of the H allele was found (p = 0.084, odds ratio = 5.309). CONCLUSIONS These findings seem to suggest that a turnover of catecholamines, connected with polymorphism determining high activity of COMT enzyme, is connected with the risk of ED occurrence, particularly anorexia nervosa. The risk is significantly higher for women with an allele of higher activity.