Hepatitis C virus(HCV)chronic infection may be associated with a great number of both hepatic and extrahepatic manifestations, in the majority of cases the underlying pathogenetic mechanisms are immune mediated, as evidence by the presence of circulating auto-antibodies and immune-complexes, including cryoglobulins, may lead to organ and non organ specific immunological alterations. Aim of the study: was to describe the patterns of disease expression in patients with systemic lupus erytheromatosis( SLE) associated with HCV infection and to analyze the epidemiology, clinical and immunological implication of this association. Setting: Zagazig University Hospitals. Subjects and methods: This study was conducted on one hundred subjects; 50 patients with SLE (fulfilled the criteria of the American College of Rheumatology) and 50 apparently healthy blood donors as a control group. All subjects were subjected to: history taking ,careful clinical examination and routine investigations including : complete blood picture ,c reactive protein,C3,C4 liver and kidney function tests and auto-antibodies [anti nuclear antibodies(ANA) double strand nuclear antibodies(dsDNA),anti Smith antigen (anti Sm) ,anti cardiolipin(ACLA) and special investigation as anti nuclear cytoplasmic antibody(ANCA), anti smooth muscle antibodies(ASMA) detection of HCV antibodies by ELISA 3 rd generation and proved by PCR for positive samples ,abdominal ultrasound and liver biopsy that was done to some patients. Results: Antibodies to HCV were present in 10 patients with SLE (20%) and 3(6%) of the blood donors studied. Among the anti-HCV-positive group, HVC infection was confirmed by PCR in 7 SLE patients (14%) and in 3 blood donors (6%) (P<0.001).In patients with HCV infection, we observed higher frequency of arthritis, serositis, nephropathy and hepatic involvement a lower frequency of neurological myositis, mucosal ulcers and cutaneous SLE features compared with SLE patients without HCV infection, as regard laboratory investigation a lower frequency of positivity for anti-dsDNA(28.5% versus 66.5%)and Anti Sm, a higher frequency of throbocytopenias, low level of C4 (53%versus 8.5%),cryoglobulins (71%versus 22%)and rheumatoid factor(71%versus11%)compared with SLE patients without HCV infection. Conclusion: The prevalence of HCV infection in SLE patients was higher than in blood donors from the same geographic area and may alter the clinical and serological manifestations of SLE.