The response of adult rabbit small intestine to the heat-stable (ST) and heat-labile (LT) enterotoxins of Escherichia coli has been investigated by employing the ligated loop technique. Fluid accumulation was determined in relation to enterotoxin dose and duration of gut exposure. The individual responses to ST and LT differed in a characteristic manner. Onset of net fluid accumulation in response to ST appeared to be immediate even at the lowest dose tested. Onset of net fluid accumulation in response to LT was rapid at high doses but delayed at low doses. Maximum volume per length ratios elicited by ST occurred between 4 and 6 h after injection of loops over the entire range of doses tested. However, maximum ratios elicited by LT occurred no less than 10 h after injection even at low doses. Fluid accumulation elicited by LT increased in duration with increasing dose; high doses of LT producing a response which was sustained for at least 18 h. The net effect of these differences in reaction characteristics is a sharp increase in the proportion of the cumulative net secretory response attributable to LT with time. Therefore, a 6-h assay time is appropriate for the titration of ST, whereas an 18-h assay is not. The 18-h assay was found more appropriate for toxin-antitoxin neutralization studies since only LT was neutralized by anti-enterotoxin serum. LT of E. coli (swine) strain P-263 and (human) strain 334 was neutralized by antibody stimulated by enterotoxin from E. coli (human) strain H-10407. LT was labile to mild acid conditions, whereas ST was not.