Ranitidine is an H2-receptor antagonist primarily used to treat peptic ulcer. The present automated solid-phase extraction technique involves sorbent conditioning of a cyano (CN) cartridge with 0.5 ml of methanol and 1.0 ml of extraction buffer (0.005 M phosphate, pH 9). Plasma samples were applied by passing 1.0 ml of plasma through the cartridge and subsequently washing with 2 ml of the extraction buffer. Appropriate larger volumes of dialysate were used to concentrate ranitidine onto the cartridge so that the amount eluted was increased to within detectable limits. Urine samples were deluted with distilled water to decrease the ranitidine concentration to within the range of the standard curve. The high-performance liquid chromatographic method (mobile phase 88-89% of 0.02 M phosphate buffer pH 3 and 11-12% of methanol; Spherisorb phenyl cartridge column, 10 cm X 0.46 cm I.D., 5 micron particle diameter, flow-rate 1.1 ml/min; detection at 228 nm) is sensitive to 2 ng/ml in 1 ml of sample. The internal standard of choice was determined to be n-propionylprocainamide as compared to cimetidine and lidocaine. The method was cost-efficient, rapid and simple due to the automated sample processing. The coefficient of variation on replicate assays was less than 10% over all concentrations studied. Recoveries were between 97 and 110%, and the method was linear over the range 1.90-687.20 with a mean correlation coefficient of 0.999.