Since being recognized in 1976 and 1983, respectively, penicillinase-producing strains of Neisseria gonorrhoeae (PPNG) and chromosomally mediated resistance (CMRNG) have attained a worldwide distribution. The high endemicity of both types of resistance in some regions precludes the continued routine use of procaine penicillin (APPG) as treatment for gonorrhea. In this study, we have evaluated 72/216 men with uncomplicated gonococcal urethritis at the venereal clinic in Mexico City. These men were part of a blinded randomized comparative study for treatment with group (P) penicillin having 33 patients and group (S) spectinomycin having 39. Efficacy with (P) was 24/33 (72.7%); nine failures retreated and were cured with spectinomycin. Efficacy with (S) was 35/39 (89.7%); four failures retreated and were cured with cefotaxime. We found correlation between MICs and resistance; all the strains with MICs of greater than or equal to 1.0 mcg/ml of penicillin failed to be cured, the MICs of greater than or equal to 32 mcg/ml of spectinomycin failed to be cured. The overall resistance to both regimens was 23/72 to penicillin (31.9%) (22 PPNG and one CMRNG) and 4/72 (5.5%) to spectinomycin.