A system involving the combination of cation exchange solid-phase extraction and gradient elution HPLC with diode array detection was developed for the isolation and identification of basic drugs in urine. At least 100 basic drugs commonly encountered in urinary drug screening and many popular illicit drugs could be identified. Detailed study of 30 of these compounds showed that in addition to the procedure's simplicity and convenience, recoveries were close to 100% in most cases. The method was compared with an existing liquid-liquid extraction/capillary gas chromatography procedure and was at least as effective for extracting and identifying basic drugs, and especially effective at extracting problematic compounds including morphine, benzoylecgonine, temazepam, and oxazepam. Additional advantages of solid-phase extraction technology include the elimination of time-consuming shaking and centrifugation steps, elimination of reusable glassware, and reduced sample-operator contact with potentially infectious samples.