A sensitive method for monitoring serum piroxicam (Feldene) is described. The assay requires 1.0 ml of specimen and involves chloroform extraction from an acidified mixture followed by concentration and injection into a liquid chromatograph. Column effluent is monitored at 330 nm. Retention times of piroxicam and the internal standard (naproxen) are 6.6 and 11.0 min, respectively. The lower limit of detection in serum is 0.5 mg/L. Within-day precision (coefficient of variation, CV) of piroxicam in serum (5-13 mg/L range) varied from 3.6 to 6.3%; between-day CV at concentrations of 5 to 20 mg/L varied from 6.5 to 9.8%. Analytical recovery of piroxicam at 20 mg/L was 88%. Several other drugs were analyzed but none interfered with the assay. Serum concentrations found in 28 patients on a 20-30 mg/day dose ranged from 1.5 to 15.2 mg/L.