Therapy of disease caused by penicillinase-producing Neisseria gonorrhoeae with lower-than-standard doses of cefoxitin was evaluated. A pilot study showed that doses of greater than or equal to 1 g were adequate, whereas 500-mg doses consistently failed. After the pilot study, 89 men with gonorrhea were treated with 1 g of cefoxitin given intramuscularly plus 1 g of probenecid given orally. Of the 89 men, 86 were cured. Sixty per cent were infected with penicillin-resistant strains of N. gonorrhoeae. The three men who were culture-positive on follow-up had been sexually reexposed, whereas none of those with negative cultures had had reexposure. These clinical results indicate that a treatment regimen of 1 g of parenteral cefoxitin plus 1 g of oral probenecid appears to be as effective as the standard 2-g dose. Regimens using doses lower than 1 g are ineffective.