In dogs with gastric and duodenal Thomas cannulas, we investigated the threshold dose range of exogenous secretin and intraduodenal HCl for pancreatic bicarbonate secretion and, with a recently developed radioimmunoassay, measured the increase in plasma secretin concentrations. Synthetic secretin (2.5, 7.5, and 22.5 ng X kg-1 X h-1) was dissolved in saline or 0.1% dog albumin and given with or without a background infusion of 30 ng X kg-1 X h-1 of caerulein. The minimal dose of secretin that elicited a significant pancreatic bicarbonate response as well as an increase in plasma secretin concentration was 7.5 ng X kg-1 X h-1 when administered with albumin and 22.5 ng X kg-1 X h-1 without albumin. The threshold dose for duodenal HCl was 2 mmol X h-1. The threshold secretin dose for bicarbonate secretion and for an increase in plasma secretin levels was unchanged with a background caerulein infusion. Furthermore, postprandial secretin concentrations were measured. After a meat meal plasma secretin release appeared to occur in spikes up to 10 pmol X l-1 corresponding to secretin levels seen during infusion of 7.5 ng X kg-1 X h-1 of secretin and intraduodenal acid perfusion at a dose of 2 mmol X h-1.