Two liquid chromatographic methods with UV detection were developed for the determination of ceftibuten in human plasma and urine. Diluted plasma samples were directly injected onto a reversed-phase column without prior protein precipitation while diluted urine samples were processed through an automated on-line sample clean-up procedure using column-switching. Both methods were linear over clinically relevant concentration ranges in plasma (from 0.1 to 50 micrograms ml-1) and urine (from 0.5 to 60 micrograms ml-1). The methods showed acceptable precision (RSD < 20%) and accuracy (bias < 15%) at the limit of quantitation (LOQ) for ceftibuten in plasma and urine. These LOQs represented the lowest concentrations of ceftibuten in plasma (0.1 micrograms ml-1) and urine (0.5 micrograms ml-1) that could be measured with acceptable precision and accuracy. RSDs for both within-day and between-day analyses were < or = 12% for plasma and < 7% for urine. These methods have been used successfully for the analysis of ceftibuten in plasma and urine following single oral doses of 200, 400 and 800 mg in man.