The ontogeny and the function of rheumatoid factors (RF) are poorly understood. Here we describe a stable neonatal hybridoma cell line of BALB/c origin that secretes a RF autoantibody of the IgM class. By a series ofin vitroassays we determined that this RF reacts specifically with the murine IgGl heavy chain. It also binds IgG of several mammalian species. By using mutant IgGl molecules, the reactive epitope was mapped to the CH3 domain of the constant region of IgGl. These findings indicate that clones with reactivity to autologous IgGl exist in normal mice at birth.