In this study, low concentrations of histamine(2)-receptor (H-2-)antagonists were effected across a water plug, with separation taking place in a binary buffer comprising ethylene glycol and NaH2PO4 (pH 5.0), and detection at 214 nm. Liquid-liquid extraction with ethyl acetate-isopropanol is shown to provide extracts that are sufficiently clean. The calibration curves were linear over a concentration range of 0.1-2.00 mug/mL cimetidine, 0.2-5.0 mug/mL ranitidine-HCI, 0.3-5.0 mug/mL nizatidine, and 0.1-3.0 mug/mL famotidine. Mean recoveries were >82%, while the intra- and interday relative standard deviations (RSDs) and relative errors (REs) were all <13%. The method is sensitive with a detection limit of 3 ng/mL cimetidine, 30 ng/mL ranitidine HCI, 50 ng/mL nizatidine and 10 ng/mL famotidine (S/N = 3, electric-driven injection 90 s). This newly developed capillary electrophoresis (CE) method was applied for the determination of analytes extracted from plasma taken from a volunteer dosing a cimetidine, ranitidine, and nizatidine tablet simultaneously. These three H-2-antagonists can be detected in real samples by this method, excluding the low dosing of famotidine tablet.