Background: Routine screening for Chlamydia trachomatis and Neisseria gonorrhoeae in men in the United States is not recommended. However, untreated men remain a potential reservoir for chlamydial and gonococcal infections and reinfection among women. Chlamydia and gonorrhea positivities and associated epidemiology were evaluated among males in the southern United States. Methods: Data were analyzed from 603 320 males, aged 15 to 60 years, who were undergoing chlamydia and gonorrhea testing in sexually transmitted disease, family planning, correctional, college, and other facilities between 2001 and 2005. Results: Males screened were primarily non-Hispanic black (63%) or non-Hispanic white (37%). Overall, chlamydia and gonorrhea positivities were both 13%. From 2001 to 2005, the chlamydia positivity increased 32% and the gonorrhea positivity decreased 28%. With increasing age, chlamydia positivity decreased, while gonorrhea positivity remained relatively stable. However, in men aged less than 30 years, both chlamydia and gonorrhea positivities were significantly higher than in men aged 30 years or greater (P < .01). Non-Hispanic blacks had a 5-fold higher risk for gonorrhea and 1.5-fold higher risk for chlamydia than non-Hispanic whites (P < .001). Men living in metropolitan statistical areas had a 1.27-fold higher risk for gonorrhea than men living in nonmetropolitan statistical areas (P < .001). Conclusions: Chlamydia and gonorrhea positivity rates were high in males in the southern United States relative to the rates among men in the United States and were influenced by demographic and geographic factors.