A high performance liquid chromatographic (HPLC) method is described for the determination of rofecoxib (RFC) in bulk drug, tablets, and human plasma samples. The methods are linear over the concentration ranges 0.005 -30.0 and 0.010- 10 mug mL(-1) in mobile phase and human plasma, respectively. Chromatography was carried out on a reversed phase Spherisorb ODSI column using a mixture of acetonitrile: methanol: 0.067 M KH2PO4 (27:20:53, v/v/v) adjusted to pH 6.95 with 3M NaOH. Detection was realized at 244 nm using a DAD detector. The retention time observed for RFC and etodolac (internal standard) at about 7.5 and 10.7 min, respectively. The proposed RP-HPLC method was validated for precision, accuracy, ruggedness, and recovery. The limit of detection was found to be 0.00143 and 0.00301 mug mL(-1) in mobile phase and human plasma samples, respectively. The proposed method allows a number of cost and time saving benefits. The described method can be readily applied for the analysis of tablets, drug dissolution studies, and human plasma samples. This method could be used without any interference from tablet matrix and endogenous substance from the plasma samples.