A method for the quantitative determination of major antidepressants in aqueous matrices by CE using ESI-MS is presented. Several aqueous, nonaquoeus, and mixed aqueous/organic solvent BGEs including inorganic and organic acids were investigated with respect to their suitability for the separation of the selected analytes. Finally, due to the necessity to employ MS detection if the developed method should be suitable also for environmental samples, only MS-compatible electrolytes were taken into account. Based on this fact optimum results were obtained with a system consisting of 1.5 M formic acid and 50 mM ammonium formate in ACN/water (85/15). Linear calibration plots could be obtained for all solutes over a concentration range of almost two orders of magnitude, and the LODs achieved were in the range of 3-6 microg/L for trazodone and 39-43 microg/L for sertraline with the TOF instrument and the single quadrupole instrument in the SIM mode, respectively. This fact allowed the assumption that the presented method can be regarded as suitable for the determination of antidepressants even in the trace amounts commonly present in environmental samples. Spiking of river water and sewage plant effluent extracts with the selected solutes showed that no interferences from the matrix usually found in such samples can be expected. Finally the quantitative determination of the seven antidepressants in environmental samples was used to benchmark the performance of CZE coupled to a single quadrupole MS and a TOF-MS.