One hundred thirty-seven evaluable patients with uncomplicated gonorrhea were treated with a single 500-mg intramuscular dose of cefotaxime. All isolates were susceptible to concentrations of cefotaxime less than or equal to 0.1 microgram/ml. The minimum concentration of cefotaxime needed to inhibit 90% of isolates was less than 0.04 microgram/ml. At follow-up, infection was eradicated in 181 of 187 (97%) infection sites. Bacteriologic cures of 100 of 101 (99%), 55 of 56 (98%), 23 of 25 (92%), and 3 of 5 (60%) were attained at the urethral, endocervical, rectal, and oropharyngeal sites, respectively. Side effects were minor, and 90% of patients rated the injection-site pain as absent or mild. A single 500-mg dose of cefotaxime is an effective, economic treatment for uncomplicated gonorrhea.