The glucose-6-phosphate dehydrogenase (G6PD) enzyme activity was determined in 299 Northern Sardinian patients with cholelithiasis. Sixteen (12.80%) of the 125 male patients studied were G6PD deficient; 33 (18.96%) of the 174 females were heterozygous and 1 (0.57%) homozygous. Thus, the prevalence of G6PD deficiency in male subjects with cholelithiasis is about 35% higher (p less than 0.02) than that of a normal male control group (7.29%). As regards female patients, the incidence of the GdMed allele was also significantly different (p less than 0.05). Thus, G6PD-deficient subjects may have a predisposition to develop gallstones, even in the absence of clinical signs of chronic hemolysis.