A simple reversed-phase high-performance liquid chromatography method using probenecid as internal standard was used for the quantitation of serum cloxacillin in eight Asian patients. The method does not require the extraction of the antibiotic from serum and the percentage recovery of cloxacillin was 96-103%. The presence of ampicillin, fusidic acid, benzylpenicillin, and gentamicin in serum appeared not to interfere with the method. The day-to-day coefficient of variation of the method over 6 months for 4-120 micrograms/ml ranged between 6.2 and 11.5%. In the eight patients in whom cloxacillin was administered intravenously or orally, there was great interindividual and intra-individual variation in the serum concentrations attained. The highest concentration of 85 micrograms/ml was obtained in a sample taken 1.5 h after an intravenous dose of 1 g. The lowest concentration of less than 1 microgram/ml was from a sample taken 6 h after an oral dose of 500 mg.