A simultaneous high-performance liquid chromatographic (HPLC) method has been developed and validated for the determination of zafirlukast and loratadine in human plasma. The assay involved the use of a solid phase extraction for plasma sample clean up prior to HPLC analysis. An Oasis HLB Bond-Elute column was used. Baseline resolution was achieved using a Symmetry C₁₈ column with mobile phase consisting of sodium phosphate buffer (pH 3.5): acetonitrile (40:60, v/v) at a flow rate of 0.8 ml/min and UV detection set at 243 nm  with montelukast as internal standard. The method was validated over the range of 25‑500 ng/ml and 5‑150 ng/ml for zafirlukast and loratadine, respectively (R² > 0.999). Recoveries were in the ranges of  93-102% at 75-400 ng/ml, 30-120 ng/ml level for zafirlukast and loratadine, respectively. The method proved to be precise (within-run precision ranged from 1.6-7.4% and between-run precision ranged from 1.3-6.7%) and accurate (within-run accuracies ranged from 1.5-5.9% and between-run accuracies ranged from 1.7-3.5%). The limit of quantitation (LOQ) and limit of detection (LOD) in human plasma were 25.0, 5.0 ng/ml and 10.0, 2.0 ng/ml for zafirlukast and loratadine (S/N = 3), respectively.