High concentrations of interferons can inhibit keratinocyte proliferation and induce the expression of HLA-DR antigen on keratinocytes. In the present study, the effects of low concentrations of recombinant human interferon alpha, beta and gamma were examined on DNA synthesis and the expression of HLA-DR and bullous pemphigoid (BP) antigens in normal human keratinocytes. Low concentrations of interferons induced DNA synthesis in normal human keratinocytes when epidermal cell growth factor and low Ca++ were used during the initial stages of culturing. This result indicates that physiological concentrations of interferons can induce keratinocyte activation.