Previous experiments have demonstrated the cholestatic effects of somatostatin administration in several animal species. These effects were confirmed in the rat. Nine pairs of intact awake rats received intravenous sodium taurocholate (23 mg hr-1) to stabilize bile flow, and half were later given somatostatin at doses of 185 micrograms hr-1. After 1 hr of somatostatin the experimental group showed a significant decrease in bile flow compared to the control group. Cholestasis reversed when somatostatin infusion was stopped. An in situ isolated perfused rat liver technique was used to assess the direct effects of somatostatin on biliary flow. In 10 pairs of rat livers, after achieving stable bile flow, half of those perfused (the "experimentals") received continuous (370 micrograms hr-1) somatostatin infusion, while the controls received saline. The percentage change in bile flow from baseline in the somatostatin group was not significantly different from that in controls for any test period. Bile analysis revealed no significant differences between groups for cholesterol, phospholipid, or bile salt concentrations or outputs. These data suggest that somatostatin inhibits bile secretion by some mechanism other than direct inhibition of bile secretory mechanisms.