To study the mechanism of salicylate-induced choleresis in rhesus monkeys, we utilized animals with indwelling common bile duct catheters under phencyclidine anesthesia. Bile flow, [14C]erythritol clearance (an estimate of canalicular flow), and bile acid secretion were measured during baseline and for 1 1/2 hr during salicylate infusion. Bile flow increased from 91.2 +/- 7.3 ml/24 hr (SEM) to 180.1 +/- 8.0 ml/24 hr (P less than 0.001) with salicylate infusion and [14D]erythritol clearance from 114.5 +/- 8.9 ml/24 hr to 222.3 +/- 10.7 ml/24 hr (P less than 0.001), but bile acid secretion was unchanged, suggesting increased bile acid-independent canalicular bile flow. Salicylate concentration in bile averaged 1.48 +/- 0.08 mmol/liter, and salicylate concentration in extra bile produced by salicylate was unlikely to result in chloeresis of the magnitude observed. [3H]inulin bile-plasma ratios, measured in these same studies, were unchanged after salicylate administration, suggesting that permeability of the biliary tree was not altered. Bile lipid secretion, like bile acid secretion, was unchanged after salicylate administration, so no change occurred in the lithogenic index of the bile. These results demonstrate that salicylate is a potent choleretic in rhesus monkeys because of enhancement of bile acid-independent bile flow. Salicylate produced no change in the lithogenic index of the bile.