The possibility that the variable severity of diarrheal disease due to enterotoxigenic Escherichia coli might be explained by quantitative differences in the activity of heat-labile enterotoxin was examined. The amount of toxin secreted by 13 enteropathogenic strains of E. coli was quantitated by measurements of the toxin-dependent increase in adenosine 3':5'-cyclic phosphate (cyclic AMP) in Chinese hamster ovary cells. The activity ranged from 150 pmol of cyclic AMP/ml per mg of protein to 4,040 pmol/ml per mg. With three representative strains there was good correlation (r = -0.999; P less than 0.05) between the amounts of cyclic AMP accumulated intracellularly (4,040, 2,071, and 470 pmol of cyclic AMP/ml per mg of protein) and the ability of the filtrate to distend the rabbit ileal loop, as measured by the amounts of toxin required to produce half-maximal distension (50% effective dose, which had values of 11.5, 27.5, and 38.5 mg, respectively). The observed strain-to-strain variation in toxin activity may explain the variation in severity of diarrheal disease caused by enterotoxigenic E. coli.