A simple, rapid, and sensitive spectrofluorometric method has been developed for the determination of olanzapine (OLZ) and fluphenazine hydrochloride (FPZ HCI). The proposed method is based on the quantitative quenching effect of the studied drugs on the native fluorescence of eosin at pH 3.4 and 3.2 for OLZ and FPZ HCI, respectively. The fluorescence was measured at 547 nm after excitation at 323 nm. The fluorescence-concentration plots were rectilinear over the range of 0.05-1.0 and 0.10-1.0 microg/mL, with lower detection limits of 1.8 x 10(-3) and 1.2 x 10(-3) microg/mL, for OLZ and FPZ HCI, respectively. The proposed method was successfully applied to the analysis of commercial tablets and ampules containing the drugs, and the results were in good agreement with those obtained with reference methods. The proposed method was further applied to the determination of OLZ in spiked human plasma. The mean recovery was 98.62 +/- 0.24% (n = 4). The method was also used for stability studies of FPZ HCI upon oxidation with hydrogen peroxide, and the kinetics of the reaction were studied. A proposal for the reaction pathway was postulated.