Concentration of sulfamethazine was measured in plasma and tissues (fat, liver, kidney, spleen, lungs, and skeletal muscle) of pigs given the drug IV and PO. The plasma concentration vs time curve was best described by a 2-compartment model, with a distribution half-life of 0.46 hour and an elimination half-life of 16.9 hours. Bioavailability after oral administration was 85.8 +/- 5.3%. The tissue and plasma sulfamethazine concentration vs time data were used to develop a multi-compartment pharmacokinetic model of sulfamethazine disposition in pigs. Plasma and tissue concentrations of sulfamethazine in pigs were measured at various intervals after multiple oral doses of sulfamethazine, and were compared to concentrations predicted by the model. Model predictions for tissue concentrations of sulfamethazine after addition of the drug to feed (110 micrograms/g of feed for 98 days; 550 micrograms/g for 30 days) were compared to results from other studies. The model accurately predicted the number of days for sulfamethazine concentration to fall below 0.1 micrograms of tissue/g (0.1 ppm, the tolerated concentration) in various tissues.