A rapid and reliable micro procedure for the high pressure liquid chromatographic analysis of cimetidine, N“-cyano-N-methyl-N‘-[2-[[(5-methyl-lH-imidazol-4-yl)methyl]thio]ethyl]guanidine, in serum or plasma is described. The percentage analytical recovery of cimetidine and internal standard (β-hydroxypropyl-theophylline) was 65 and 99%, respectively. The between-day precision of the method at cimetidine serum concentrations of 2,000, 1,000, and 500 μg/liter yielded coefficients of variation of 10.6, 11.5, and 10.6%, respectively. The method has been used in preliminary studies to determine the serum concentrations in patients receiving the drug by both the oral and intravenous route.