A new capillary electrophoresis (CE) method was developed and validated for the screening of human urine for nineteen drugs of abuse. In order to achieve sufficient separation, the electrolyte composition was modified using beta-cyclodextrin (beta-CD) and organic solvents. To process each sample, a sequential injection-solid-phase extraction (SI-SPE) system was constructed. Using this device, matrix clean-up, extraction, and preconcentration of analytes were performed onto a C(18) cartridge. Optimal separation and detection were obtained using a background electrolyte consisting of 100mM phosphate adjusted to pH 6.0, with 20 mM beta-CD, 5% acetonitrile and 20% isopropanol. Electrokinetic injection was performed at 5 kV for 10s, separation voltage was 25 kV and column temperature was set to 25 degrees C. The separation was carried out in a 67.0 cm x 50 microm fused-silica capillary with UV detection at 214 nm. The combination of SI-SPE and sample stacking showed significant sensitivity enhancement with limits of detection in the range of 5-30 ng ml(-1). A validation study showed good reproducibility of both migration time (RSD=0.003-0.088%) and peak area (RSD=0.54-4.8%). Overall, this automated and miniaturized SI-SPE system provides a rapid, sensitive, and robust procedure for analysis; as well as minimizes sample and solvent consumption.