In view of the recent discovery of penicillinase-producing strains of Neisseria gonorrhoeae in Zambia, the efficacies of single intramuscular doses of aqueous procaine penicillin G (4.8 x 10(6) units plus 1 g of oral probenecid) and 2 g of spectinomycin were evaluated in an open clinical trial of the treatment of acute gonococcal urethritis in men. The former regimen was given to 123 men; failure of treatment was observed in 9.1% of the 88 men followed for two weeks. Spectinomycin was given to 124 men; treatment failure occurred in 3.8% of the 104 men followed for two weeks. During the trial, 190 unselected isolates of N. gonorrhoeae were screened by rapid iodometric test, and two penicillinase-producing strains were detected. MICs of penicillin and spectinomycin were determined by the agar dilution method for 110 and 98 isolates, respectively. MICs of penicillin of greater than or equal to 0.125 micrograms/ml were observed with 78.2% of the strains, while 83.7% had MICs of spectinomycin of less than or equal to 15.0 micrograms/ml. It was suggested that penicillin be given routinely for treatment of gonorrhea in Zambia and that spectinomycin be reserved for treatment of gonococcal infections not cured by penicillin.