A simple, accurate and sensitive high pressure liquid chromatographic technique is described for the determination of fluoxetine in the capsule dosage form, human plasma and in biological fluid. Analysis is performed with a reversed phase-C18 column with ultraviolet detection at 228 nm. The isocratic mobile phase (1.5 ml/min.) consists of acetonitrile and triethylamine buffer (48 + 52, V/V). A linear calibration model (correlation coefficient 0.99863) was developed using pyridoxine as internal standard. The retention times were 2.10 and 3.20 min for pyridoxine and fluoxetine, respectively. The method was applied for the quantitation of fluoxetine in spiked human plasma samples. The detection limit is 5 microg/l and the absorbance varies with fluoxetine concentrations in the range (10-300) microg/l. The mean % recovery +/- S.D. was found to be 97.99% +/- 2.39. The proposed method was applied successfully for monitoring of fluoxetine in human plasma after single dose administration of one prozac capsule.