Carbamazepine and diphenhydramine interfered with the assays of haloperidol and its metabolite, reduced haloperidol, by reversed-phase HPLC. Retention times of haloperidol, reduced haloperidol, and the interfering drugs were very sensitive to the percentage of potassium phosphate buffer in the mobile phase as well as to the final pH of the eluant. Retention times were not very dependent upon ionic strength of the eluting solvent mixture. Haloperidol and reduced haloperidol in the range of 0.5–10 ng/mL were analyzed in the presence of 0.2 µg/mL diphenhydramine and 5 µg/mL of carbamazepine. The concentrations of all drugs used were in their expected therapeutic ranges. The isocratic chromatographic conditions were as follows: 25-cm × 4.6-mm C-18 column; mobile phase, 75% phosphate buffer (final concentration, 0.06M) and 25% acetonitrile; final pH, 3.5; flow rate, 2.5 mL/min; and detection by UV absorption at 220 nm. Additional changes in the percent buffer in the mobile phase may be useful in achieving separation of other interfering compounds.