Strains of Neisseria gonorrhoeae requiring arginine, hypoxanthine, and uracil (Arg-Hyx-Ura-) are highly susceptible to penicillin G, and have been associated with asymptomatic urethral infection and disseminated gonococcal infection (DGI). The authors recovered Arg-Hyx-Ura- strains from 48% of 282 heterosexual men and women, versus only 9% of 69 homosexual or bisexual men (P less than 0.0001). In a separate population of consecutive men with urethral gonococcal infections, urethral discharge was absent in 0 of 96 homosexual men, versus 18 of 261 heterosexual men (P less than 0.025). Homosexual men accounted for none of 41 cases of DGI in men in 1970--1973, compared with 35% of men with uncomplicated gonorrhea in 1978. These findings suggest that asymptomatic urethral gonococcal infection and DGI are uncommon in homosexual men, perhaps because infection with Arg-Hyx-Ura- strains is relatively uncommon. Screening cultures of urethral specimens for N. gonorrhoeae had a low yield among homosexual men in the population studied. Strains of N. gonorrhoeae recovered from homosexual men were significantly more resistant to penicillin than were isolates from heterosexual subjects; this was true even for non-Arg-Hyx-Ura-strains. This difference may help to explain the lesser efficacy of ampicillin in treatment of rectal gonococcal infection in homosexual men.