Clonidine, an alpha 2-adrenergic agonist, has been shown to be useful in the treatment of some patients with chronic diarrhea. Previous animal and human studies have suggested that clonidine alters both small bowel fluid absorption and total gut motility. We measured the effect of clonidine 0.3 mg on oro-cecal transit time, using the lactulose-breath hydrogen test. Intestinal transit time in six normal healthy male volunteers after administration of clonidine was 148 +/- 20 min, and was 90 +/- 7 min with a placebo (p less than 0.05). The average prolongation in transit time was 69.5%. We conclude that clonidine may markedly alter human small intestine transit time which explains, at least in part, the mechanism for this agent's antidiarrheal effect.