Nifedipine has been shown to inhibit small bowel motility and to increase ileal water and electrolyte absorption in animals, but few reports are available in human subjects. The drug has been reported to influence esophageal and colon motility in man, without affecting gastric emptying. We performed a double-blind, controlled, crossover, randomized study to investigate the effect of oral nifedipine 30 mg vs placebo on the orocecal transit time of a lactulose-labeled, liquid caloric meal in nine healthy volunteers, and its correlation with plasma nifedipine concentration. The transit time was measured using the breath hydrogen test. The drug study was preceded by a reproducibility study, which showed a mean variation in transit time of 8.3% (+/- 1%, SE). Nifedipine significantly increased orocecal transit time compared to placebo (nifedipine 131 +/- 16; placebo 104 +/- 14.5 min; P < 0.05). This effect correlated well with plasma nifedipine concentration expressed as area under the curve (r = 0.92, P < 0.004). Nifedipine 30 mg significantly delays orocecal transit of a liquid caloric meal. The small bowel is likely to be the site of action. These findings may afford a rational basis for investigating a possible antidiarrheal role of nifedipine.