We describe a rapid, sensitive, and expedient radial-compression liquid-chromatographic method for routine quantification of etoposide (VP-16-213) in plasma of cancer patients undergoing chemotherapy with this agent. Teniposide was used as the internal standard. The mobile phase was a mixture of 10 mmol/L phosphate solution and methanol (50.7/49.3, by vol), adjusted to pH 3 with phosphoric acid. The flow rate was 2 mL/min. We used a 5-micron particle size C18 cartridge with a radial-compression separation system. The effluent was monitored with an electrochemical detector. Plasma samples are extracted with chloroform and the chloroform is evaporated. The residue, reconstituted in mobile phase, is injected onto the cartridge. Assay results were linearly related to concentration (r greater than 0.9944) over the range examined, 0.010-28.0 mg/L. The intra-run CV was less than 4.4%, and we encountered no interference from anticancer drugs or other compounds. We present data for plasma sampled at different intervals from two cancer patients being infused with etoposide.