A simple, specific and rapid reversed-phase high-performance liquid chromatographic (HPLC) procedure for sotalol determination is described requiring small plasma volumes. The high recovery of sotalol from plasma and the high precision of measurement obviate the need for an internal standard. Plasma samples (300 microliters) were deproteinised with 50 microliters of 70% (w/w) perchloric acid in disposable glass tubes. After vortex-mixing and centrifugation, 30 microliters of 4 M K2HPO4 were added followed by gentle shaking. A 20-microliters aliquot was then injected (by autosampler) for HPLC analysis. Chromatography was performed on a glass-lined 250 mm x 4 mm 5-micron C18 steel column. The mobile phase was 6% (v/v) acetonitrile in 0.08 M KH2PO4 buffer (pH 4.6). The flow-rate was 0.8 ml/min. Detection was by fluorescence with excitation and emission wavelengths at 235 and 310 nm, respectively. The retention time for sotalol was 7.1 min. Calibration was linear from 0.16 to 10 micrograms/ml in plasma (r greater than 0.999 for detector response to sotalol). The minimum concentration for quantitation was 0.08 micrograms/ml [within assay coefficient of variation (C.V.) less than 5%]. Recovery was near quantitative (greater than 98%) and replicate (intra-assay precision was less than 5% C.V.). Analysis of samples (n = 10) at concentrations of 0.42 and 4.2 micrograms/ml gave mean values of 0.44 and 4.3 micrograms/ml, respectively. The inter-assay C.V. values were 4.5 and 2.2%, respectively. Other clinically used antiarrhythmic drugs did not interfere. This assay can be performed using other commercial C18 analytical columns by suitable adjustment of mobile phase flow-rate and acetonitrile composition.