Abstract: A HPLC method for determination of piroxicam in serum and application of this method to piroxicam disposition studies in man were described. The piroxicam was extracted from acidified serum with diethyl ether using phenacetin as internal standard. A RP YWG-C18 (10μm) column fitted with a 254 nm UV detector was used for analysis; the mobile phase was 0.2 M acetate buffer-methanol (1:1 v/v). The sensitivity of the method was 0.05 μg/ml serum. Assay linearity was demonstrated over the range of 0.1～10 μg/ml of serum with a regression coefficient of 0.9998. The assay recovery was 99.28%, and no interferences were found from endogenous compounds or other commonly used antiinflammatory agents. For the serum concentration following oral administration of piroxicam tablet to healthy volunteers (n=10), the best fit was found to be with a one compartment model. After administration of 20 mg dose, the parameters, which were close to the data reported in literature, were as follows: T_m=4.19 h, C_m=2.8760μg/ml, AUC=144.064 μg.h.ml^-1, T 1/2 (K_A)=0.75h, T 1/2 (K_B)=40.57 h. The long half-life of piroxicarn in man suggests that one-daily dosing may be appropriate for maintaining therapeutic serum levels.