During an epidemic caused by sulfonamide-resistant group A Neisseria meningitidis (A SuR strain), rifampin (600 mg per day for four days) or minocycline (100 mg every 12 hr for five days) was administered as chemoprophylaxis to 1,540 unvaccinated recruits in the Finnish Armed Forces. Rates of carriage of all strains of N. meningitidis were initially reduced by 78% (from 60% to 13%) in the 389 men receiving rifampin and by 62% (from 70% to 26%) in the 1,151 men receiving minocycline but rose to approximately 30% in both groups four weeks after prophylaxis. The carriage of A SuR strains was similarly reduced. An individual follow-up of 636 trainees demonstrated a high rate of new infections. It is suggested that the long-term inefficiency of rifampin and minocycline is due to their inability to reduce the carriage rates enough to prevent further spread of infection after prophylaxis is descontinued. However, no new cases appeared among the men receiving the prophylaxis. Five strains highly resistant to rifampin were found after the use of rifampin (minimal inhibitory concentration, greater than or equal to 100 microgram/ml), but no minocycline-resistant strains were encountered. No unpleasant side effects were seen in subjects receiving either drug.