Uncomplicated acute gonorrhea in 200 cases, 100 of each sex, was treated with a single oral dose of 900 mg rifampicin. The failure rate was 12.5%. The treatment was compared with 1.0 MU of benzyl penicillin and 1.5 MU of procaine penicillin in a single intramuscular injection given to 200 other cases of acute uncomplicated gonorrhea, 100 of each sex. The failure rate was 3.5%. The difference in failure rate between the two treatments is significant. Remarkably quickly after one dose of oral rifampicin in 11 out of 25 cases a high degree of rifampicin resistance developed in the gonococcal strains. Thus for epidemiological reasons the use of rifampicin in the treatment of gonorrhea could quickly lead to the spread of rifampicin-resistant gonococcal strains in the community, and rifampicin must be advised against in gonorrheal therapy, at least as a first hand choice in patients with a penicillin allergy.