We report the successful desensitization to cefotaxime in a patient with severe lumbar osteomyelitis of unknown bacteriology and hypersensitivity to the drug. Desensitization was carried out because of the unknown bacteriology, the favorable response to cefotaxime at that time, and hypersensitivity to other antibiotics. On the first day the patient received 1 mg cefotaxime intravenously. The dose was increased for 13 successive days to 4 g cefotaxime intravenously per day. No allergic reaction occurred during desensitization or within 4 weeks of observation under this therapy. Patients with severe infections of unknown bacteriology might benefit from desensitization if therapy with a second-choice antibiotic is impossible.