Methods for the determination of flurbiprofen and ibuprofen in dog serum were developed using high-performance liquid chromatography and automated serum extraction. Sample extraction was automated by use of cartridges packed with a styrene-divinylbenzene macroreticular resin in a microprocessor-controlled centrifugal system. The average recoveries were 98.9% for flurbiprofen and 94.5% for ibuprofen. The limits of detection were approximately 0.04 microgram/ml for flurbiprofen at 254 nm and 0.5 microgram/ml for ibuprofen at 230 nm. The relative standard deviations for the determination of a laboratory standard between days was 2.4% (20 microgram/ml) for flurbiprofen and 1.7% (13 microgram/ml) for ibuprofen. Peak height ratios were linear with concentrations of 0.04--100 microgram/ml for flurbiprofen and 1.0-50 microgram/ml for ibuprofen. These methods are simple, rapid, sensitive, and specific. The use of an automated sample preparation procedure improved the between-day precision by a factor of two when compared to a manual extraction procedure. These methods were applied to bioavailability studies in dogs.