Variability in the bioavailability of orally administered trimethoprim due to Magnesium trisilicate and Kaolin-pectin has been investigated. The concentration of trimethoprim in blood was determined spectrofluorometrically at 0, 15 and 30 minutes and 1, 2, 4 and 6 hours. The area under the blood concentration curve of trimothoprim was significantly decreased, when the drug was given concurrently with magnesium trisilicate or kaolin-pectin. The mean decrease in maximum blood concentration of trimethoprim in magnesium trisilicate and kaolin-pectin treated groups was 49.94% and 29.42% respectively. The data suggest that a clinically significant interaction may occur due to concurrent administration of trimethoprim with these drugs.