Ninety-eight patients with the gonococcal arthritis-dermatitis syndrome were prospectively treated with penicillin G, at least 10 million units intravenously per day, followed by ampicillin, 2.0 g orally per day, to complete at least 10 days of treatment (33 patients); ampicillin, 3.5 g orally plus probenecid 1.0 g, followed by ampicillin, 2.0 g per day orally for at least 7 days (29 patients); lower doses of parenteral penicillin G (20 patients); oral tetracycline (6 patients); parenteral cephalosporins (5 patients); and other regimens (5 patients). The response to treatment was equally rapid and complete in each group. At least 90% of the patients in each group had subjective improvement and defervescence within 2 days, and all patients followed for at least 2 weeks achieved complete clinical and bacteriologic cure. Patients with purulent synovial effusions improved significantly more slowly than patients with nonpurulent effusions or with no effusions, regardless of which treatment was used.