An accurate, reliable procedure was developed for kinetic and therapeutic monitoring of paroxetine in human plasma. Steady-state plasma levels of paroxetine were measured for 18 geriatric patients (mean age 75) in a double-blinded study. Paroxetine doses ranged from 10 to 40 mg/day. The assay was suitable for patients on concurrent medications, and a small sample volume (1 ml) of patient plasma was used with sufficient sensitivity and specificity. After extraction and separation on a Beckman, Ultrasphere 5-microm C18 column (150x2 mm I.D.), the recovery (mean+/-S.D.) for paroxetine was determined to be 86.5+/-5.2%. The limit of quantitation for paroxetine in this assay was 5 ng/ml. Inter-assay reproducibility (C.V.) for the patient samples and quality controls ranged from 3.7 to 7.6%.