In recent years a rising incidence of syphilis has been observed, especially in the population of homosexual men. Because of altered sexual behavior in terms of increased promiscuity paralleled by decreased use of condoms and the fact that a syphilis infection increases the susceptibility to HIV coinfection, the incidence of HIV is also rising once again in this population. In patients with HIV coinfection, the course of syphilis is often atypical or dramatic. Stage-specific features suggesting coinfection include prolonged primary ulcers persisting well into the secondary stage, numerous atypical cutaneous findings in the second stage and a rapid progression from stage to stage. The diagnosis of syphilis may be more difficult because of false positive or false negative serological findings in patients with HIV coinfection. Whether or not the CNS is more often involved is this patient group has not been established by prospective studies and remains controversial. However, WHO and CDC recommendations include evaluation of the CSF in HIV-infected patients with either late syphilis or when the time course is unknown period. There is worldwide agreement on the therapy of syphilis in patients with HIV coinfection. Patients with early syphilis should be treated with 2.4 benzathine penicillin i.m. once or twice; patients with late syphilis, twice or three times. Patients presenting with clinical or serological signs of neurosyphilis require 18-24 million IU penicillin i.v. daily for at least 2 weeks.