The penetration of oral cefixime into the synovial fluids of 16 patients (mean age, 50.6 years) who underwent joint taps for rheumatic noninfectious disorders was examined. The patients were each given a single dose (400 mg) 2 to 24 h prior to the tap. Cefixime concentrations in serum and joint fluid samples were measured by high-performance liquid chromatography, and the bactericidal activities of these fluids against three isolates each of Haemophilus influenzae and Escherichia coli were examined. The highest concentrations in serum and synovial fluid were achieved 4 h following drug intake, the mean values being 2.8 and 2.03 micrograms/ml, respectively. Effective bactericidal activities (bactericidal titer, > 1:2) against E. coli and H. influenzae were demonstrated in serum and joint fluid up to 10 h following oral intake of cefixime. These results suggest that cefixime penetrates well into joint fluid, achieving levels above the MIC for E. coli lasting as long as 10 h and levels above the MIC for H. influenzae lasting up to 24 h after administration. Good bactericidal activity against susceptible bacterial isolates was observed for at least 10 h after dosing.