In this micro-scale method for liquid-chromatographic measurement of cimetidine in 250-microL volumes of plasma or gastric fluid, a combination of organic- and aqueous-phase extractions, and protonation of the internal standard and cimetidine, enabled us to detect 2.0 ng of cimetidine on the column. We also used a radial compression module, which reduced the retention times for cimetidine and the internal standard to only 2.78 and 2.00 min. The speed and sensitivity of this method facilitates analysis of large numbers of samples.