Four cephalosporins, cefazolin, ceftizoxime, cefaloridine and cefaclor, were determined using a novel microbore high-performance liquid chromatographic system designed to be entirely compatible with direct liquid interfacing (DLI) for mass spectrometric analysis. The chromatographic support was a 5-micron C18 column of 0.3 mm I.D., compared with the usual microbore column diameters of 1-2 mm. The mobile phase contained no buffers or salts which may have caused column blocking or mobile phase crystallization, and the use of a concentration column allowed the injection of large volumes of analyte (up to 500 microliters). The assay was reproducible, the relative standard deviations being less than 20% within-day and between-day for all the drugs. The detection limit for cefaloridine and cefazolin was 1 ng and for cefaclor and ceftizoxime 5 ng.