Chemoprophylaxis with antibiotics is both feasible and desirable for prevention of a potentially serious disease when specific groups at risk can be defined and when a safe, effective, and affordable prophylactic agent is available. Although the Advisory Committee on Immunization Practices recommends rifampin for prophylaxis of meningococcal disease, there are failures of treatment and adverse reactions associated with the administration of this drug, and it cannot be used during pregnancy. In 1987, during an outbreak of group A meningococcal disease in Saudi Arabia, the efficacy of a single intramuscular dose of ceftriaxone was compared with the standard regimen of rifampin for eradication of pharyngeal carriage of Neisseria meningitidis among persons at risk. Follow-up cultures indicated successful eradication for 97% of those who received ceftriaxone and 75% of those who received rifampin. Thus, although ceftriaxone exceeds rifampin in fulfilling the criteria for an effective prophylactic agent, recommendations regarding its use still must be made with caution because of limited clinical experience.