A rapid method for the isolation and high-performance liquid chromatographic (HPLC) determination of sulfamethazine (SMZ) in pork tissues (kidney, liver, and muscle) without using organic solvents is developed. The isolation is performed by homogenization with an acid solution using an ultrasonic-homogenizer, followed by centrifugation. The HPLC analyses are performed using a reversed-phase C(4) column (150- x 4.6-mm i.d.), a mobile phase of 0.02 mol/L citric acid solution, and a photodiode array detector. The resulting HPLC chromatograms are free from interferences for determination and identification. The proposed technique is shown to be linear (r > 0.99) over the concentration range 0.1-2.0 microg/g for all pork tissues. Average recoveries of SMZ (spiked 0.1-2.0 microg/g) range from 87.6% to 90.2%, with inter- and intra-assay variabilities of less than 4%. The total time required for the analysis of one sample and limit of quantitation is less than 20 min and 0.09 microg/g, respectively.