Exocrine pancreatic response to duodenal perfusion with alkaline solutions (pH 11.4) was studied in the anaesthetized rabbit; secretin and vasoactive intestinal polypeptide (VIP) levels in portal plasma were measured and the contribution of cholinergic mechanisms was also evaluated. Intraduodenal perfusion of sodium carbonate stimulated flow rate and bicarbonate output to a maximum of 322 +/- 44 and 609 +/- 105% respectively compared with basal levels. Significant increases of plasma secretin levels, with a maximum of 267 +/- 38% as compared with basal, were also observed. A lower increase in VIP levels (maximum of 151 +/- 12%) was seen. All these effects, except the VIP response, were substantially inhibited by atropine. Our results show that exocrine pancreatic response to intraduodenal sodium carbonate is specifically focused on hydroelectrolytic secretion. Keeping in mind what occurs after intraduodenal alkaline phosphate buffer administration (at the same pH as sodium carbonate: 11.4) it seems that about 50% of the pancreatic response to sodium carbonate may be ascribed to pH and the remaining 50% to the carbonate anion. Moreover, this response would mainly be mediated by secretin, whose release can be facilitated by a cholinergic reflex.