Treatment of WISH (human amnion) cells with interferon-gamma (IFN-gamma) inhibits their growth. Release of the cells from IFN-gamma-mediated growth inhibition led to a rapid and significant increase in DNA synthesis, followed by doubling of cell numbers. The DNA synthesis profile was strikingly similar to that shown by WISH cells released from growth arrest by the G1/S phase inhibitor, aphidicolin. This strongly suggested that IFN-gamma treatment leads to growth inhibition of WISH cells at the G1/S boundary of the cell cycle. In contrast, IFN-alpha blocked growth of these cells at the G0/G1 boundary.