The association between alcohol-induced disorders of human spermatogenesis and four restriction fragment polymorphisms (DraI, MspI, PstI and RsaI) of the cytochrome P450 2E1 gene was investigated in an autopsy study on 254 men. Acquaintances were interviewed and the mean daily alcohol consumption of the subjects was calculated on the basis of the interviews. Spermatogenesis score and testicular morphology were assessed by light-microscopy, and cytochrome 2E1 polymorphic genotypes were determined using the polymerase chain reaction. Of the 204 heavy-drinking men, 42 (20.6%) men had normal spermatogenesis (p < 0.001, compared to moderate drinkers). Partial spermatogenic arrest was observed in 76 (37.3%) men and complete spermatogenic arrest in 79 (38.7%) men (p < 0.001, compared to moderate drinkers), whereas seven men (3.4%) had Sertoli cell only syndrome. The overall allelic frequencies for the common and rare polymorphic alleles were 0.98 and 0.02 (MspI) and 0.99 and 0.01 (PstI and RsaI), respectively. No associations between heterozygosity in the MspI, PstI or RsaI loci, or the allelic frequencies of common and rare alleles, and disorders of spermatogenesis were observed. The allelic frequencies for the common and rare polymorphic alleles in the DraI locus were 0.90 and 0.10, respectively. No significant difference was observed, either among moderate or heavy drinkers, in the frequency of the rare allele between men with disorders of spermatogenesis and those with normal spermatogenesis in the respective group, although men with disorders of spermatogenesis in general had a slightly lower frequency of the rare allele when compared to those with normal spermatogenesis. In conclusion, we were unable to demonstrate a significant association between any polymorphisms in the CYP2E1 gene and disorders of spermatogenesis. RsaI, MspI and PstI polymorphisms were extremely rare in our population and could thus possibly be excluded as reasons for genetic susceptibility to disorders of spermatogenesis in our series.