A sensitive high-performance liquid chromatography method with electrochemical detection for the determination of olanzapine in human plasma is described. Olanzapine from plasma samples was isolated by a simple one-step liquid--liquid extraction with 15% methylene chloride in pentane with an extraction recovery of approximately 94% of the total olanzapine in plasma. The compound was separated on a cyano column. Under the conditions described, commonly coadministered drugs and other common antipsychotic drugs did not interfere with the analysis of olanzapine. The lower limit of determination of the assay was 0.25 ng of olanzapine per ml when 1 ml of plasma was used for the analysis. The interaassay and intraassay variance was (CV%) less than 10%. The standard curve was linear within the range of 0.25 to 50 ng/ml of olanzapine. This method has been used for the determination of plasma levels of olanzapine in patients with schizophrenia who were treated with daily oral doses of 10, 15, and 20 mg of olanzapine. The results indicate that the plasma level of olanzapine increases linearly with the administered daily oral dose (r = 0.6889, p = 0.01).