There are limited data about false-positive reactions against hepatitis C virus (HCV) in syphilitic patients and false-positive reactions against syphilis in the patients with HCV infection, The aim of this study was to demonstrate the false-positivity of syphilis in patients with HCV infection, the false-positivity of anti-HCV in patients with syphilis and the validity of the serological tests in such patients. Fifty patients with positive anti-HCV, 21 patients with positive VDRL and 50 healthy subjects were studied. Syphilis serology was determined by the Venereal Disease Research Laboratory (VDRL) test and microhemagglutination for T. pallidum (MHA-TP) test. Hepatitis C serology was determined by a second generation ELISA (Ortho Diagnostics) test for HCV antibody, and anti-HCV positive patients were tested for HCV RNA by polymerase chain reaction (PCR). All assays were performed on all subjects. Not only the false-positive VDRL reaction in the patients with HCV infection but also false-positive anti-HCV tests in syphilitic patients have been observed. Four patients with syphilis had positive anti-HCV and negative HCV-RNA, whereas 10% (5 of 50) of patients with hepatitis C infection had positive VDRL and these patients were negative for MHA-TP test, The rates of false-positivity of VDRL and anti-HCV were higher than within the control group (p<0.05). According to these data, positive anti-HCV in syphilitic patients and positive VDRL in chronic hepatitis C may be false-positive results with regard to the reaginic tests, Therefore, therapeutic measures should not be initiated without confirmation with a treponemal test or PCR. VDRL and HCV-ELISA tests may be interacted with IgM or IgG antibodies. This relationship should be investigated in further studies.