The role of antibiotics in the treatment of iatrogenic discitis remains controversial. This study was carried out to assess the ability of cephazolin (a first-generation cephalosporin) to penetrate the intervertebral disc and to establish the role of intravenous antibiotics in the prevention and treatment of iatrogenic discitis. Six sheep had 1 g of intravenous antibiotic administered between 30 minutes and 120 minutes before being killed. Two adjacent lumbar intervertebral discs were harvested and assayed for antibiotic concentration. Cephazolin could only be detected in the animals killed at 30 minutes. Intravenous cephazolin was administered 30 minutes before bacterial inoculation in 46 discs of nine sheep. In five animals, the bacterial suspension contained radiographic contrast and, in four sheep, reconstituted chymopapain. No evidence of discitis was found at any level at death. Eight sheep were treated with intravenous cephazolin commencing 1, 2, or 3 weeks after bacterial intradiscal inoculation and for periods of up to 21 days. All discs developed discitis, and the lesions appeared to be similar, irrespective of time between inoculation and the commencement, duration, and dosage of antibiotic therapy. Our study supports the use of a suitable broad-spectrum antibiotic during any surgical procedure that invades the intervertebral disc. Antibiotics, however, are unable to arrest the progression of discitis once it is established