Early diagnosis of HIV infection in the child of an HIV-infected mother may be difficult as HIV-specific immunoglobulin (Ig) G antibodies are transmitted to the fetus transplacentally. In an attempt to provide a new, simpler tool for early identification of HIV-infected children we analysed the HIV-specific IgC subclass pattern during the first year of life. One hundred and one samples were collected from 35 children born to HIV-seropositive mothers, among whom 18 seroreverted during follow-up and 17 were HIV-infected (two Pl and l5 P2 according to the Centers for Disease Control classification). Serum HIV-specific lgG3 was detectable at least in one sample in 26 out of 35 children. All 17 HIV-infected children showed persistently detectable specific lgC3, both with stable or progressive disease. Out of the l8 uninfected children who seroreverted during follow-up, nine were HIV-specific lgC3-negative when first tested and nine lost HIV-specific-lgG3 within 28 weeks after birth. The correlation of the serological results with clinical information and any other diagnostic tool on each child suggests that the clearance of specific-lgG3 antibodies heralds seroconversion in uninfected passive antibody-carrier children. This observation provides the basis for a new, simple and effective method for early diagnosis of HIV infection in children born to seropositive mothers.