The re-emergence of syphilis among HIV-infected patients has been reported in recent years. We evaluated co-infection among heterosexual immigrants in an Israeli AIDS center. The records of 1060 HIV-infected patients were evaluated for positive syphilis serology between the years 2000 and 2005, and all seropositive patients were further evaluated.s We found 150 HIV/syphilis co-infected patients (57% men, 93%of African origin), of who 135 were found to have late latent syphilis. Lumbar puncture (LP) was performed in 51 patients, 16 (31%) had abnormal cerebrospinal fluid (CSF) compatible with neurosyphilis. Abnormal CSF correlated with the absence of previous anti-syphilis treatment, but not with CD4 count, viral load or Venereal Disease Research Laboratory titres. Penicillin was recommended to all patients according to their disease stages and 81 patients completed 12 months post-treatment follow-up. Twentyone of 81 (26%) treatments were successful, 33 (41%) showed 'serofast reaction' and 27 (33%) failed therapy. In conclusion, a high incidence of syphilis with CSF reactivity suggestive of neurosyphilis was observed in heterosexual Ethiopian HIV-infected patients. Thus, repeated serological screening and CSF evaluation seems to be indicated in these patients. Penicillin therapy resulted in 'serofast reaction' or treatment failure for most patients. More, intensive treatment might be needed for HIV/syphilis in co-infected patients, especially those with severe immune-deficiency and prolonged syphilis infection.