Disseminated gonococcal infection occurs in 1%-3% of patients with gonorrhea in Seattle. Most strains of Neisseria gonorrhoeae recovered from patients with disseminated gonococcal infection are susceptible to less than or equal to 0.015 mug of penicillin G/ml. Strains susceptible to less than or equal to 0.015 mug/ml, whether isolated from patients with disseminated gonococcal infection or from those with uncomplicated infection, did not grow on chemically defined medium prepared with several lots of agar, whereas less susceptible isolates grew well. Use of methanol-extracted nontoxic agar permitted growth of the penicillin-susceptible strains and demonstrated that all of them required arginine, hypoxanthine, and uracil (Arg-Hyx-Ura-) for growth. These Arg-Hyx-Ura- strains accounted for 89% of the cases of disseminated gonococcal infection in Seattle, 38% of uncomplicated infections in Seattle, 18% of infections in Milwaukee, and none of 104 uncomplicated gonococcal infections acquired in the Philippines and Taiwan, where disseminated gonococcal infection is unusual. Regional variations in the prevalence of these Arg-Hyx-Ura- strains may correlate with regional variations in the incidence of disseminated gonococcal infection. The genetic, physiologic, and immunologic bases for concurrence of penicillin and agar susceptibility. Arg-Hyx-Ura- phenotype, and association with disseminated gonococcal infection remain undefined, as do host factors that determine whether or not disseminated gonococcal infection will result in patients infected by such strains.