BACKGROUND: Mother-to-child transmission of hepatitis C virus (HCV) has been reported in around 5% of cases, and is much more likely to occur in case of coinfection with HIV. However, other cofactors influencing the vertical transmission are still debated. AIM: To assess the serum concentration of endogenous interferon (IFN) during pregnancy, and its eventual role on the vertical transmission of HCV. METHODS: Forty-seven HCV-infected pregnant women, and 3 control groups: (1) 75 HCV-negative pregnant women; (2) 29 HCV-positive nonpregnant women; (3) 29 HCV-negative nonpregnant women entered into the study. Endogenous IFN was assayed by enzyme-linked immunosorbent assay. The following parameters were also analyzed: viral load, HIV infection, risk factors for acquiring HCV, parity, gestational age, mode and course of delivery. RESULTS: Vertical transmission of HCV was observed in 2 cases (4.3%). Plasma levels of IFN were significantly higher in HCV-positive pregnant women compared with either HCV-positive and HCV-negative nonpregnant women. The 2 mothers who transmitted the infection had IFN levels within the same range as the women who did not transmit the infection. CONCLUSIONS: In HCV-positive pregnant women, there is an increased production of endogenous IFN-alpha. Further studies are warranted for clarifying the mechanisms of this cytokine in the prevention of HCV transmission.