Concentrations of ceftriaxone in serum and intervertebral disc tissue were determined with high-pressure liquid chromatography in forty-five patients after a single intravenous loading dose of 1000 milligrams given at different intervals before an operation on the spine. The mean serum concentrations in this study corresponded well with reported values. The mean tissue concentrations were 5.6 micrograms per gram (95 per cent confidence interval, 3.6 to 6.8 micrograms per gram) one to less than two hours after administration of the antibiotic, 6.4 micrograms per gram (95 per cent confidence interval, 2.8 to 10.0 micrograms per gram) two to less than four hours, and 3.6 micrograms per gram (95 per cent confidence interval, 0.6 to 6.6 micrograms per gram) at fourteen to less than sixteen hours. These drug concentrations exceed the minimum inhibitory concentration that was effective against 90 per cent of the bacteria for methicillin-sensitive Staphylococcus aureus; for Streptococcus pyogenes, agalactiae, viridans, pneumoniae, and bovis; and for community-acquired Enterobacteriaceae. The average serum-to- tissue ratio was 191:1 at less than one-half hour and 13:1 at less than one and a half hours. The lower values of the 95 per cent confidence intervals for the concentration of the antibiotic exceeded the minimum inhibitory concentrations in the disc tissue against most susceptible bacteria during the period between one and a half and four hours, but a larger bolus would be needed to maintain this level for a longer period (such as in a longer operation) and as prophylaxis against methicillin-sensitive Staphylococcus aureus and coagulase-negative staphylococci.