A high performance liquid chromatography method with uv detection was developed for the quantitation of pseudoephedrine in human plasma in the presence of guaifenesin. The method involved a sample preparation technique based on solid phase extraction, followed by evaporation, reconstitution in water and injection into the HPLC system. The HPLC system consisted of a C8 column and a 70:30 V/V 0.03M sodium heptane sulfonate : acetonitrile as the mobile phase, ultraviolet detector at 220 nm and (±)α-(methylaminomethyl) benzyl alcohol (MAMBA) as the internal standard. The concentration-response relationship for pseudoephedrine was found to be linear over a concentration range of 25 ng/ml to 450 ng/ml, with a lower limit of detection of 20 ng/ml and a lower limit of quantitation of 25 ng/ml. The coefficient of variation for inter-day ranged from 5.7% to 10.5% with a mean of 8.3% over the concentration range of 70–450 ng/ml. The coefficient of variation for intra-day ranged from 1.1% to 5.1% with a mean of 4.4% over the same concentration range. The mean percent recovery of pseudoephedrine from plasma was 90%. In addition, this method was specific in the presence of guaifenesin.