A rapid, specific, and sensitive high performance liquid chromatographic method for the simultaneous analysis of eleven tricyclic imipramine-derived drugs has been developed by using a Lichrosorb RP Select B column, an isocratic system at ambient temperature, and UV detection at 230 nm. The influence of acetonitrile and methanol content, the molarity of sodium acetate, and the effect of adding counter-ion in the mobile phase have been investigated. Excellent separation of a mixture of the eleven compounds was accomplished within 30 minutes. The method was applied to pharmaceutical dosage forms containing a single active ingredient; any of the other compounds can be used as internal standard since these drugs are structural analogues and are generally not found simultaneously. Satisfactory results were obtained both for the recovery and the coefficient of variation.