The effect of oral cimetidine or ranitidine on the pharmacokinetics of the nonsteroidal anti-inflammatory agent flurbiprofen was studied. Nine healthy volunteers participated in the study. The subjects were divided into three groups, and each group alternated therapy with each of the following treatments: flurbiprofen 200 mg (two 100-mg tablets), flurbiprofen 200 mg plus ranitidine 150 mg two times daily for seven days before and for two days after receiving flurbiprofen, and flurbiprofen 200 mg plus cimetidine 300 mg four times a day for seven days before and for two days after receiving flurbiprofen. Blood samples were collected at time zero and at various intervals during a 48-hour period. Serum flurbiprofen concentrations were determined by high-performance liquid chromatography. No significant differences in elimination rate constant, peak concentration, time to peak concentration, volume of distribution, or elimination half-life were noted among treatments. The difference in area under the curve (AUC) in subjects treated with flurbiprofen alone and in those treated with flurbiprofen plus cimetidine was significant. Two subjects experienced gastric upset; one case was apparently caused by cimetidine, and the other was likely caused by flurbiprofen. Although a significant increase in AUC was observed in subjects receiving flurbiprofen plus cimetidine, the interaction is probably not clinically important.