A Bolivian population of squirrel monkeys, Saimiri sciureus, exhibits several features of Gilbert's syndrome in man, and is proposed as a nonhuman primate model of the condition. The Bolivian population was found to have higher fasting (40.6 f 2.7 pM; mean f S.E.) and postcibal (9.9 f 0.9 p M ) plasma unconjugated bilirubin concentrations (p c 0.001) than a closely related Brazilian population (fasting 5.5 f 0.7 pM); postcibal (2.4 f 0.7 pM). After intravenous administration of ['H]bilirubin as a tracer dose or at 3.4 pmoles per kg body weight, there was delayed plasma clearance in the Bolivian monkeys. Hepatic UDP-glucuronyl transferase activity for bilirubin (164 f 25 nmoles per 30 min per gm liver) and biliary bilirubin diglucuronide to monoghcuronide ratios (2.9 f 0.2) were lower in Bolivian monkeys than in Brazilians (421 f 36 nmoles per 30 min per gm liver-p < 0.01 and 4.1 f 0.1-p c 0.02, respectively). Hepatic cytosol glutathione-S-transferase B activity (ligandin) levels were similar for the two populations. After phenobarbital therapy, fasting (11.1 f 0.9 phf) and postcibal (5.3 2 1 p M ) plasma bilirubin concentrations in Bolivian monkeys were significantly reduced (p < 0.001). Sulfobromophthalein clearance was slightly slower in the Bolivian than in the Brazilian monkeys. SGOT, lactate dehydrogenase, y-glutamyl transpeptidase and alkaline phosphatase activities were not increased in Bolivians. Fasting serum conjugated bile salt concentrations in Bolivian monkeys were lower than that in Brazilian monkeys (p c 0.01). Erythrocyte survival and hematological measurements were comparable in both populations.