Dogs fed a marginal protein, high carbohydrate diet containing borderline amounts of methionine consistently develop pigment gallstones, marked taurine deficiency, and abnormal secretion of unconjugated bile salts. Since taurine is essential for normal secretion of bile salts in the dog, a species that cannot use glycine for bile salt conjugation, we hypothesized that taurine deficiency plays an important role in the pathogenesis of canine pigment gallstones. The rates of formation of pigment gallstones at 6 weeks were compared in dogs fed normal dog chow, lithogenic diet alone, and lithogenic diet supplemented with either taurine or methionine (45-55 mg/kg/day). No dog fed normal dog chow, but 11 of 12 dogs fed lithogenic diet, formed pigment gallstones and sludge. Supplementation of the lithogenic diet with taurine did not protect against pigment gallstones; five of six dogs developed gallstones and sludge. However, supplementation with methionine was protective, only one of six dogs was found to have a few flecks of pigmented material in its gallbladder. Interestingly, neither taurine nor methionine protected against previously observed increases in the concentrations of biliary calcium and bile salt profile indicating that at least some of the abnormalities previously observed in this model are not related to methionine/taurine deficiency. These results disprove our initial hypothesis that taurine deficiency plays an important role in the pathogenesis of pigment gallstones, but did show that a lack of methionine is linked to the formation and growth of canine pigment gallstones. The mechanism(s) leading to the formation of gallstones in dogs that are methionine deficient are is not clear from these studies.