Sucralfate has been reported to protect the gastroduodenal mucosa against a variety of agents and is known to adsorb bile salts. Since gastrointestinal side effects can seriously compromise the efficacy of nonsteroidal anti-inflammatory drug therapy, and since it seems reasonable to assume that sucralfate may adsorb nonsteroidal anti-inflammatory drugs, the influence of sucralfate on the pharmacokinetic parameters of naproxen was assessed in 12 healthy volunteers. To do so, the pharmacokinetic profile of naproxen, administered alone or with sucralfate, singly or repeatedly (twice daily for five days), was compared. No significant difference was observed with any pharmacokinetic parameter between the single administration of naproxen alone or with sucralfate. However, a significantly lower maximum plasma concentration was attained with the repeated administration of naproxen in combination with sucralfate, compared with the repeated administration of naproxen alone. When single- and multiple-dose administration were compared, significant differences were observed in the maximum plasma concentration and the cumulative area under the curve. These results suggest an accumulation of naproxen after five days' administration. This accumulation, however, is not altered by the administration of sucralfate. The results of this study suggest that when naproxen is administered with sucralfate, only a delay in naproxen's absorption may occur, confirmed by a lower maximum plasma concentration, a longer time to reach the maximum plasma concentration, a similar elimination half-life, and equivalence in bioavailability. The clinical importance of such a delay has yet to be proved; however, it is unlikely that the clinical efficacy of naproxen will be altered, since the amount of drug absorbed remains the same.