The association between alcohol-induced disorders of human spermatogenesis and glutathione S-transferase-M1 genotype was investigated in an autopsy study comprising 271 subjects, including interviews with relatives or close acquaintances on the alcohol consumption of the deceased. Of the 50 moderate drinking men (reported mean daily alcohol consumption < 40 g), 21 (42.0%) had normal spermatogenesis, whereas 24 men (48.0%) had partial, and five (10.0%) complete arrest of spermatogenesis. Of the 21 men with normal spermatogenesis, nine (42.9%) had GST M1 'null' genotype, while this genotype was found in 13 (44.8%) of the 29 men with partial or complete spermatogenic arrest. Of 212 heavy-drinking men (reported mean daily alcohol consumption > 80 g), only 45 (21.2%) had normal spermatogenesis, whereas 77 (36.3%) had partial spermatogenic arrest. Complete arrest of spermatogenesis was found in 81 men (38.2%) and nine men had Sertoli-cell-only syndrome (4.2%). Of the 45 heavy drinkers with normal spermatogenesis, 27 (60%) men had GST M1 'null' genotype (OR 2.7 with 95% confidence intervals: 1.0-4.0, when compared to those with disorders of spermatogenesis). The frequency of GST M1 'null' genotype in heavy drinkers with normal spermatogenesis also differed from that of corresponding moderate drinkers, whereas the frequency of GST M1 'null' genotype in heavy drinkers with disorders of spermatogenesis was similar to moderate drinkers with or without disorders of spermatogenesis. The finding that > 20% of men in the heavy-drinking group had normal spermatogenesis suggests individual variations in sensitivity to alcohol-induced disorders of this process. Heavy drinkers with GST M1 'null' genotype were slightly less prone to develop disorders of spermatogenesis. Thus, the GST M1 locus may be associated with susceptibility to develop alcohol-induced disorders of spermatogenesis.