A sensitive, specific, high-performance liquid chromatographic procedure is described for the simultaneous determination of procainamide and its metabolite, N-acetylprocainamide, in plasma. Basic plasma (2.0 ml), containing pheniramine maleate as an internal standard, is partitioned with methylene dichloride. The organic extract is concentrated to between 0.3 and 0.5 ml, and 100-microliter aliquots are chromatographed on a microparticulate silica gel column using 0.1% acetic acid-20% 0.1 M ammonium acetate in acetonitrile as the mobile phase. With a fixed-wavelength (254-nm) UV detector, both compounds can be quantitated in the 0.1-8.0-microgram/ml of plasma range.