We here present the clinical cases of two homosexual patients, carriers of human immunodeficiency virus (HIV), who later presented a syphilis infection and who after receiving the usually recommended treatment, suffered a relapse of the infection six months afterwards, with neurologic involvement in one case. The clinical characteristics are discussed as well as the diagnostic and therapeutic problems which syphilis infection presents in HIV infected patients. Serological results are comparable to those of the general population, although face positives have been occasionally reported as well as some abnormally elevated titers. It is possible that neurosyphilis might be more frequent and of earlier appearance in HIV infected patients. Therefore, it might be necessary to carry out a spinal fluid exam, in these type of patients, in order to rule out the existence of an early and/or asymptomatic neurologic affectation and give the appropriate antibiotic treatment.