The effect of various antacids on the absorption of tolfenamic and mefenamic acids has been investigated in three separate crossover studies, each consisting of four phases. Single doses of magnesium hydroxide (85 mg, 425 mg and 1700 mg) or of water (150 ml) were given by mouth to 6 healthy volunteers immediately after tolfenamic acid 400 mg (Study 1), and, using an identical study design, after mefenamic acid 500 mg (Study 3). In Study 2 sodium bicarbonate 1 g, aluminium hydroxide 1 g, an antacid preparation containing both aluminium and magnesium hydroxides, or water alone were ingested with tolfenamic acid 400 mg. Plasma concentrations of tolfenamic and mefenamic acids and their cumulative excretion in urine were determined up to 24 h. Magnesium hydroxide greatly accelerated, in a dose-dependent manner the absorption of both tolfenamic and mefenamic acids. The peak times in plasma were shortened by about 1 h by 425 mg and 1700 mg magnesium hydroxide, and the peak plasma concentrations of both fenamates were elevated up to 3-fold. The area under the plasma concentration-time curve between 0 and 1 h of tolfenamic acid was increased up to 7-fold and that of mefenamic acid up to 3-fold. The total bioavailability of tolfenamic and mefenamic acids was only slightly increased. Aluminium hydroxide alone and in combination with magnesium hydroxide significantly retarded the absorption and lowered the peak plasma concentration of tolfenamic acid. Sodium bicarbonate had no significant effect on its absorption. The interaction with magnesium hydroxide leads to higher and earlier peak plasma concentrations of the fenamates.(ABSTRACT TRUNCATED AT 250 WORDS)