Lippman and coworkers recently reported striking response rates achieved in patients with cervical cancer using a combined treatment with 13-cis-retinoic acid and interferon-alpha. In vitro studies demonstrated a synergistic amplification of proliferation inhibition by retinoids and interferon in malignant cells. Comparing all-trans- with 9-cis-retinoic acid, the latter was more effective in inhibiting tumor cell growth and in inducing synergism with interferon-gamma. Combination of retinoic acid with interferon-gamma increased the down-regulation of specific binding sites of interferon-gamma. Expression of MHC class II antigens induced by interferon-gamma was not further enhanced by retinoic acid. These results indicate that interferon seems to modulate the retinoic acid system.