Background: Psoriasis is a chronic, currently incurable immune-mediated skindisease. Activated T cells, monocytes, and pro-inflammatory cytokines, mostnotably interferon alpha (IFN-α) and interferon gamma (IFN-γ) have all beenshown to play pivotal roles in the pathogenesis of psoriasis. Studies have reportedhigh prevalence of hepatitis C infection (HCV) among patients with psoriasis.Objectives: To study serum levels of interferon-α and γ in psoriatic patients withand without hepatitis C infection compared to HCV patients and healthy controlsin an attempt to shed some light on the possible roles of interferon-α and γ in theassociation reported between these two diseases.Patients and methods: Twenty patients with psoriasis and HCV (group 1), 25patients with psoriasis only (group 2) , 20 patients with HCV (group 3) and 24 ageand sex matched healthy controls (group 4) were recruited from the dermatologyand endemic medicine outpatient and inpatient clinics of Cairo university hospital.Serum samples were obtained and serum interferon-α and γ levels were estimatedby ELISA technique.Results: Serum IFN-αlevels were significantly elevated in psoriatic patients withor without HCV infection (group 1 and 2) when compared to control group ( p <0.05 , p<0.001) respectively. Yet these levels did not correlated with PASIscore(p>0.05). Serum IFN- γ levels were significantly lower in HCV patients alonewhen compared to control group(p<0.001). They were also lower in psoriaticpatients with HCV when compared to psoriatic patients alone (p<0.001). Moreover, serum IFN- γ levels were high in group 1 and 2 when compared to healthy control( p<0.001). Yet, serum IFN- γ levels did not correlated with PASI score (p> 0.05).Conclusions: High levels of serum IFN-α and IFN-γ did not correlate with PASIscore, indicating that they have a role in psoriasis but not the main regulators or sole players in its pathogenesis. Lower IFN-γ level in patients with isolated chronicHCV infection suggest impairment of IFN-γ production which plays an importantrole in persistence of infection, chronicity of inflammation and evolution infibrosis.