CD4 cell counts and blood plasma and seminal plasma human immunodeficiency virus type 1 (HIV-1) concentrations were compared in HIV-1 RNA-seropositive men with urethritis and with or without genital ulcer disease (GUD). GUD was associated with lower CD4 cell counts (median, 258 vs. 348/microL) and increased blood plasma HIV-1 RNA (median, 240 x 10[3] vs. 79.4 x 10[3] copies/mL). Men with nongonococcal urethritis and GUD shed significantly greater quantities of HIV-1 in semen (median, 195 x 10[3] vs. 4.0 x 10[3] copies/mL) than men with nongonococcal urethritis without GUD. These levels decreased approximately 4-fold following antibiotic therapy. The results indicate an association between GUD and increased blood HIV-1 RNA levels. Increased HIV-1 in semen was demonstrated in some men with GUD; such an increase could lead to increased transmission, thus complicating interpretation of the role of the genital ulcer itself in the infectiousness of HIV. Reasons for increased HIV RNA in semen in men with GUD remain to be determined.