ENTEROTOXIGENIC strains of Escherichia coli elaborate two enterotoxins, a heat-labile toxin (LT) and a heat-stable toxin (ST), which cause diarrhoeal disease in humans¹; ST-producing E. coli cause diarrhoea in adult volunteers² and have been associated with epidemic diarrhoea in a nursery for the newborn³ and with sporadic adult diarrhoea among North American tourists to Latin America⁴ and the Navajo people in Arizona⁵. LT-producing strains are identified by the ability of culture filtrates to cause fluid accumulation in rabbit ileal loops at 18 h (ref. 6) or by morphological alteration of Chinese hamster ovary (CHO) cells⁷ or of Y-l adrenal cells⁸. ST-producing strains are identified by the ability of culture filtrates to cause earlier fluid accumulation in rabbit ileal loops (peak accumulation at 6 h (ref. 6), or by fluid accumulation in the gut of the suckling mouse at 3 h (refs 9, 10). LT acts in a manner similar to cholera toxin (CT) by activating adenylate cyclase¹¹. The mechanism of action of ST is unknown, however. Culture filtrates of a strain of E. coli that produced both LT and ST caused immediate net fluid secretion in canine jejunal segments without the 1-h delay characteristic of the response to CT^12,13. In addition, culture filtrates caused an immediate increase in canine jejunal adenylate cyclase activity as measured by enzymatic generation of P³²-cyclic AMP from P³²-labelled ATP¹³, also in contrast to the delay in appearance of increased adenylate cyclase activity following exposure to CT¹². The possibility that the early effect of ST was mediated by changes in cyclic nucleotide concentrations was investigated; culture filtrates of ST-producing strains of E. coli caused increased cyclic GMP concentrations in rabbit intestinal tissue and the cyclic GMP analogue 8BrcGMP mimicked ST in magnitude and time course of intestinal fluid accumulation in both rabbits and suckling mice.