The influence of food and water intake on mefenamic acid (N-2,3-xylylanthranilic acid) bioavailability from commercial capsules of high bioavailability was studied in four healthy male volunteers. The drug was administered as a single oral dose of 250 mg, under fasting or nonfasting conditions, and a 4 X 4 Latin-square design was used. Eight blood samples were collected over a 24-h period following drug administration, and the drug plasma concentrations were determined by HPLC. The bioavailability of mefenamic acid from capsules was markedly influenced in the fasting subjects by the water but not by the food intake. A good correlation was found between the bioavailability and amount of water ingested with the drug in the fasting subjects. The area under the plasma concentration-time curve (AUC0-infinity) of mefenamic acid was highest when the capsule was taken with 50 mL of water or immediately after a meal. Increasing the amount of water from 50 to 500 mL in the fasting subjects caused a significant reduction in AUC0-infinity.