In 2000, the rate of primary and secondary (P&S) syphilis in the United States was 2.1 cases per 100,000 population, the lowest since reporting began in 1941. From 2001 to 2004, the P&S syphilis rate increased to 2.7, primarily as a result of increases in cases among men who have sex with men (MSM). To characterize the recent epidemiology of syphilis in the United States, CDC analyzed national notifiable disease surveillance data for 2000-2004, focusing on 2003-2004. This report describes the results of that analysis, which indicated that the disparity between syphilis rates among blacks and whites in 2004 increased for the first time since 1993 and is associated with a substantial increase of syphilis among black men. Syphilis rates continue to increase among MSM. After declining for 13 years, the rate of P&S syphilis in 2004, compared with 2003, increased in the South and remained the same among women. The findings underscore the need for enhanced prevention measures among blacks and MSM. In addition, enhanced surveillance is needed to detect any early increases in P&S syphilis among women.