A simple, rapid and simultaneous analytical method is described for the detection of Sulfonamide and Tetracycline residues, i.e., Sulfamerazine (SMR), Sulfamethazine (SMT), Sulfamonomethoxine (SMM), Sulfadimethoxine (SDM), Sulfaquinoxaline (SQN), Oxytetracycline (OXY), Tetracycline (TC), Chlortetracycline (CTC). Blank control and sulfonamide and tetracycline fortified fish muscle samples (0.5 g) were blended with octadecylsilyl (C,e, 40 gm, 21% load, 60Å) derivatized silica packing material (2 g). Blended fish samples were washed with hexane, then, benzene and dichloromethane were used for the elution of tetracycline and sulfonamide, respectively, The eluants containg tetracycline and sulfonamide were analyzed by HPLC. Correlation coefficients of standard curves for individual sulfonamide and tetracycline isolated from fortified samples were linear (0.9993±0.0003-0.9997±0.0003, 0.9493±0.078-0.9753±0.036), respectively, The average percentage recoveries of sulfonamide and tetracycline ranged as 80.86-96.52% to 85.88-92.23%, and 30.01-37.12% to 65.89-73.40%, for the concentration range (0.1--1.0 ppm) examined, respectively. Limit of detection for sulfonamide was 0. 05 ug/g, then, tetracycline was 0.1 ug/g. Detection of quantitation of sulfonamide residue was 0.0012 ppm for SMR in Paralichthys Odiuacleus and 0.0020 ppm for SMR, 0.015 ppm for SMM in Cyprinus Carpio. The applicability of this procedure is demonstrated by separation and detection of incurred tetracycline and sulfonamide residues in fish muscle tissue.