The stability of paclitaxel with either ondansetron hydrochloride or ranitidine hydrochloride during simulated Y-site injection at room temperature was studied. Triplicate test solutions of paclitaxel 0.3 and 1.2 mg/mL were admixed 1:1 with ondansetron 0.03 and 0.3 mg/mL (as the hydrochloride salt) or ranitidine 0.5 and 2.0 mg/mL (as the hydrochloride salt). Also, paclitaxel 1.2 mg/mL was admixed 1:1:1 with ondansetron 0.3 mg/mL and ranitidine 2.0 mg/mL. The solutions were stored in glass containers at room temperature, and samples were removed at zero, one, two, and four hours for immediate assay. At the time of the assay and before any dilution, each sample was visually inspected for clarity, color, and precipitation, and the pH was determined. Drug concentrations were measured by stability-indicating high-performance liquid chromatographic procedures. Throughout the study, more than 90% of the initial concentrations of paclitaxel, ondansetron, and ranitidine remained in the solutions. No precipitates, color changes, or haziness was seen. The changes in pH were minor. Paclitaxel in concentrations of 0.3 and 1.2 mg/mL was stable when mixed with either ondansetron (0.03 or 0.3 mg/mL, as the hydrochloride salt) or ranitidine (0.5 or 2.0 mg/mL, as the hydrochloride salt) and stored in glass containers for four hours. Paclitaxel 1.2 mg/mL was also stable when mixed with both ondansetron 0.3 mg/mL and ranitidine 2.0 mg/mL and stored in glass containers for four hours.