OBJECTIVES: To describe trends in the notification of infectious syphilis in New South Wales, the characteristics of homosexually active men recently notified with early syphilis, and the seroprevalence and incidence of syphilis, as well as associated risk factors, in a Sydney cohort of HIV-negative homosexually active men. DESIGN, SETTING AND PARTICIPANTS: Secondary analysis of New South Wales infectious syphilis surveillance data from 1998 to 2003; a case series of 57 homosexually active men diagnosed with early syphilis in inner Sydney from December 2002 to January 2004; and a prospective cohort study of syphilis among 1333 HIV-negative homosexually active men in Sydney recruited from June 2001 to December 2003. MAIN OUTCOME MEASURES: Rates of notification of infectious syphilis in New South Wales and in areas of inner Sydney; behavioural and clinical features of men with syphilis in the case series; and incidence of syphilis and hazard ratios (HRs) associated with sexual behaviours in the cohort study. RESULTS: Infectious syphilis notifications in inner Sydney rose more than 10-fold (from 6 in 1999 to 162 in 2003), and the increase was confined to men. Of 57 men with early syphilis in the case series, 54% were HIV-positive and 32% reported no symptoms of syphilis. These 57 men were highly sexually active and likely to report recreational drug use. In the cohort study, 1292 men (97% of participants) consented to syphilis testing; the incidence of syphilis was 0.78 per 100 person-years, and risk factors included reporting unprotected anal intercourse with HIV-positive partners (HR, 5.31; 95% CI, 2.00-184.93) and insertive oral sex (HR, 4.55; 95% CI, 1.14-18.18). CONCLUSION: Syphilis has been re-established among homosexually active men in Sydney, and HIV-positive men are over-represented. Frequent screening is needed in this population to curb the transmission of both syphilis and HIV.