In 32 patients the concentrations of sulfamethoxazole and trimethoprim in whole blood, plasma and skin blister fluid were studied in the course of treatment with co-trimoxazole and trimethoprim alone. Measurements were taken on the fourth day of treatment, 3 h after administration of the morning dose of the drug. The blood contained a lower concentration of sulfamethoxazole than plasma. About 70% of the sulfonamide penetrated into the exudate from plasma. Trimethoprim administered conjointly with sulfamethoxazole to a higher degree penetrated skin blister fluid to a greater extent than when given alone.