AbstractSimple and rapid spectrophotometric methods have been developed for the microdetermination of fluoxetine HCl. The proposed methods are based on the formation of ion-pair complexes between fluoxetine and bromophenol blue (BPB), bromothymol blue (BTB), bromocresol green (BCG), and bromocresol purple (BCP) which can be measured at optimum λmax. Optimization of reaction conditions was investigated. Beerșs law was obeyed in the concentration ranges of 0.5–8.0 μg mL−1, whereas optimum concentration as adopted from the Ringbom plots was 0.7–7.7 μg mL−1. The molar absorptivity, Sandell sensitivity, and detection limit were also calculated. The most optimal and sensitive method was developed using BCG. The correlation coefficient was 0.9988 (n = 6) with a relative standard deviation of 1.25, for six determinations of 4.0 μg mL−1. The proposed methods were successfully applied to the determination of fluoxetine hydrochloride in its dosage forms and in biological fluids (spiked plasma sample) using the standard addition technique.