A method for the determination of sulfamethazine at the 0.5 ppm level by high performance liquid chromatography (HPLC) has been shortened and simplified by use of a mini-column clean-up procedure. Fortified feed samples were extracted with acetonitrile, concentrated, and redissolved in the mobile phase. Sulfamethazine was separated from most extraneous material by a mini-column of C18/Porasil B and AX/Corasil, and analyzed by HPLC at 254 nm. Liquid standard solutions were used to fortify four formulated swine feeds and corn sample each at three levels, giving an average recovery of 98% and a relative standard deviation of 7.3%. Tests were run using 32 antibiotics and drugs to determine if they would interfere. Most of these substances were not eluted under the conditions used. Compounds which absorbed at the wavelength used did not interfere with the sulfamethazine peak.