The effects of ethanol on exocrine pancreatic amino acid transport and secretion were investigated during perfusion of the isolated rat pancreas with ethanol concentrations ranging from 0.06% to 4.1%. Amino acid transport was quantitated using a rapid dual isotope dilution technique in which unidirectional substrate uptake (15-20 sec) is assessed relative to an extracellular tracer. Pancreatic secretion evoked by 0.3 microM carbachol was abolished during perfusion with 0.32% ethanol. Influx of L-lysine, L-serine and methylaminoisobutyric acid (MeAIB) was marginally increased by 0.32% ethanol but significantly inhibited during subsequent perfusion with 1.28-4.1% ethanol. Pancreatic oxygen consumption and effluent PCO2 levels decreased with increasing ethanol concentration, and the control venous pH (7.21 +/- 0.01, n = 8) gradually approached arterial pH values (7.46 +/- 0.02, n = 9). These results indicate that low concentrations of ethanol readily inhibit secretagogue-induced pancreatic secretion. Amino acid transport at the basolateral membrane of the exocrine pancreatic epithelium appears only to be inhibited after acute exposure to high ethanol concentrations.