Among men and women treated in Seattle for uncomplicated gonorrhea with single doses of 2.4 and 4.8 million units, respectively of aqueous procaine penicillin G, treatment failure was noted within one week in 15.4% of men and in 10.4% of women. Failure rates were reduced significantly to 1.8% of men and 3.7% of women when 1.0 g of oral probenenicid was given simultaneously with the penicillin injections. The risk of failure was dependent on the resistance to penicillin of Neisseria gonorrhoeae isolated before treatment. Failure rates, which can be expected when penicillin is used without probenecid, have been calculated for each level of gonococcal resistance to penicillin and can be used in other regions to predict the efficacy of these doses of penicillin.