A high-performance liquid chromatography (HPLC) method has been developed for the rapid evaluation of minocycline concentrations in serum after chemical pleurodesis. Elution was performed with a Nova-Pak phenyl reverse-phase column and a Waters radial compression module. No organic extraction or evaporation of samples is required. The assay is linear from 0.6-20 micrograms/ml with recovery rates > or = 98%. Interassay variability is 8.2 +/- 1.1% and intraassay variability is 2.1 +/- 0.3%. Correlation coefficients were > or = 0.999 for five standard curves. The technique was effective for quantitation of serum minocycline levels in a human patient who had received the drug intrapleurally on two consecutive days. This HPLC method may be useful for monitoring adverse effects related to serum concentrations of the drug during pleurodesis.