The haptoglobin allele frequencies and the phenotype distribution were determined in 741 male Caucasian workers, aged 35 to 59 years. The association of the haptoglobin polymorphism with various clinical and biochemical parameters was investigated. Furthermore a possible interaction with the apo E polymorphism on lipid and lipoprotein traits was analysed. The frequency of Hp1 and Hp2 was found to be 0.401 and 0.599, respectively. The observed distribution of Hp types (Hp 1-1, 15.5%; Hp 2-1, 49.3%; Hp 2-2, 35.2%) was in Hardy-Weinberg equilibrium. Age, body mass index, smoking, alcohol intake and blood pressure were comparable between the three Hp groups. Subjects with Hp 2-2 had significantly higher serum total and free cholesterol concentration compared to those in other haptoglobin types (P = 0.006 and P = 0.003). Similarly, apo B levels were significantly higher among Hp 2-2 individuals (P = 0.02). No significant differences were demonstrated between the Hp phenotypes in HDL cholesterol, apo A-I, apo E, Lp(a), cholesteryl esters, fibrinogen and C-reactive protein concentrations, although for the latter an increase was noticed in Hp 2-2. The effects of Hp type and apo E type on Lp(a) and on free cholesterol levels were found to be significantly multiplicative, with the highest free cholesterol values observed in subjects having Hp 2-2 and the apo epsilon4 allele. Significantly lower Lp(a) levels were observed in individuals carrying Hp 1-1 and an epsilon2 allele than in subjects without the epsilon2 allele. In conclusion, haptoglobin polymorphism may play an important role in the regulation of lipoprotein metabolism and could contribute to the risk of coronary heart disease. Larger samples are needed to clarify the clinical relevance of the gene-gene (Hp-apo E) interaction on lipids and lipoproteins.