Pancreatic secretion was studied in anaesthetized rats tested immediately after surgery or in conscious rats tested 48 hr after the cannulation of the pancreatic duct. Pancreatic flow, protein output and enzyme output were measured over a 30-min period in the unstimulated state and after the intravenous injection of bolus doses of cholecystokinin-pancreozymin (CCK-PZ) ranging from 1.25 to 20 Crick-Harper-Raper units (CHRU). Each animal received three doses of CCK-PZ, as either ascending or descending doses. In anaesthetized rats there was a linear relationship between the log-dose of CCK-PZ and the flow, protein and enzyme output with both the ascending and descending doses. In contrast, in conscious rats flow was unaffected by CCK-PZ, and protein output was greatest after the first dose, whether this was given in the ascending or descending doses. At all CCK-PZ levels flow in anaesthetized rats was less than that seen in conscious animals, but at doses of CCK-PZ above 5.00 CHRU protein output was greater in anaesthetized rats than in conscious rats. Ultrastructural studies of the pancreas showed areas of focal cytoplasmic degeneration and possible blockage of the duct with cellular debris after administration of high doses of CCK-PZ to conscious rats. These changes may be responsible for the reduced protein output with the second and third dose of CCK-PZ in these animals. No such changes were seen in anaesthetized rats after similar doses of CCK-PZ. These studies show fundamental differences in the response of the pancreas to CCK-PZ in anaesthetized and conscious rats. The mechanism for this difference is not clear, but it may represent a change in the normal response to CCK-PZ in the anaesthetized rats as a result of the effects of acute operative trauma, possibly acting through changes in pancreatic blood flow.