Solid-phase microextraction (SPME) combined with gas chromatography (nitrogen-phosphorous selective detection) was investigated as a sample preparation technique for the assay of neuroleptic and antidepressant drugs in human plasma. A mixture of 250 µl of human plasma, water, internal standard and aqueous NaOH was extracted with a 100-µm-polydimethylsiloxane-fiber. Fibers were used repeatedly in up to 75 analyses. The recoveries of the analytes in plasma were found to be lower than 7 % after 30 min of extraction. However, in spite of the low recoveries the analytes were well separated and the calibrations were linear within the terapeutic windows of the drugs. The within-day and between-day precisions were investigated. No interfering drug was found. The influence of the concentration of proteins, triglycerides and salts, i.e. changes of the matrix on the peak areas and peak-area ratios were studied. The method is not impaired by physiological varieties in the composition of the matrix. Good agreement was found with LLE-GLC- and HPLC-standard methods for spiked and patient samples, respectively. It is concluded that the method can be used in the therapeutic drug monitoring of clozapine, levomepromazine, clomipramine, olanzapine and clomethiazol.