The priming effect of carbachol on glucose-, arginine- and glucose plus GLP-1 (7-36)amide induced insulin secretion was investigated. The isolated rat pancreas was perfused in vitro during a basal period of 10 min with Krebs-Ringer-bicarbonate buffer containing 2.8 mmol/l glucose. This medium was then supplemented with carbachol (10,1.0.1 mumol/l, respectively). After an additional 10 min period at 2.8 mmol/l glucose insulin secretion was stimulated for 44 min with 10 mmol/l glucose, or glucose plus GLP-1 (7-36)amide (0.5 nmol/l), or arginine (10 mmol/l). Pretreatment with carbachol resulted in a concentration dependent sensitization of B-cells to a consecutive glucose load (10 mmol/l). Both phases of the biphasic insulin secretory response were significantly enhanced. Priming experiments followed by a subsequent combined glucose / GLP-1 (7-36)amide or arginine stimulation were performed with 10 mumol/l carbachol. Prior exposure of the pancrease to carbachol enhanced the glucose / GLP-1 (7-36)amide induced insulin release, but left the arginine stimulated secretion unaltered. Our data suggest that in the regulation of postprandial insulin release cholinergic sensitizing effects might be involved which are mediated by muscarinic receptors.