One side-effect of the therapeutic use of antimicrobial agents is respiratory paralysis as a result of inhibition of skeletal neuromuscular transmission; cholinergic neuro-effector motor transmission in the gastrointestinal tract is inhibited by the same classes of antimicrobial agent. Study of the effects of several classes of antibiotic compound on intestinal motility has suggested that antibiotic-induced alterations of intestinal motility may be related to the onset of diarrhoea or the development of antibiotic-associated colitis. These compounds may, however, also initiate or exacerbate diarrhoea by altering control of epithelial function, a possibility that has not previously been rigorously investigated. This series of experiments investigated the effect of six antibiotics on rabbit distal colonic epithelial ion transport. Of all the antibiotics studied, only ampicillin was without effect. Clindamycin, erythromycin, gentamicin and lincomycin, each reduced the response of the epithelium to electrical field stimulation. In addition, the lincosamides clindamycin and lincomycin reduced basal short circuit current and the epithelial response to acetylcholine. Vancomycin had no effect on the response to electrical field stimulation or acetylcholine but enhanced the secretory action of prostaglandin E2. These data suggest that, in addition to their ability to alter intestinal motility, a number of potential antibiotic interactions with the epithelium and its innervation may contribute to the pathogenesis of antibiotic-associated diarrhoea and colitis.