The effects of Eschericihia coli heat-stable enterotoxin, STb, on the jejunum of pigs (three to six weeks old) and rats (250 to 350 g) were examined. In vivo and in vitro techniques consisting of ligated loops, perfused segments and isolated enterocytes were employed in the study. STb induced secretion or decreased absorption of water, sodium, potassium and chloride in vivo. Soybean trypsin inhibitor significantly increased the STb induced secretion of water in the perfused rat intestine. This suggests that trypsin-like compounds present in the jejunum reduce the activity of STb. Neither the influx of calcium nor the influx or efflux of chloride was altered by STb in the isolated enterocytes;Clonidine reduced or reversed the effect of STb on water and electrolyte transport in the pig perfusion and ligated loop studies. Morphine displayed similar effects in the ligated loops of pigs. Neither drug had any effect in the ligated loops of rats. The muscarinic antagonist 4-Diphenylacetoxy-N-methyl piperidine (4-DAMP) reduced the effect of STb on water transport in rat intestine while pirenzepine, also a muscarinic antagonist, exhibited no effect;Leucine and methionine enkephalin and loperamide had no effect on the secretory effect of STb in rat ligated intestinal loops. Chloride absorption under the influence of STb was increased by the addition of hexamethonium and scopolamine in pig ligated loops.