We studied the binding of 125I-labeled human interferon-α to peripheral blood mononuclear cells and the activity of 2′,5′-oligoadenylate synthetase in peripheral blood mononuclear cells obtained from 21 patients with chronic hepatitis B who were treated with human interferon-α or interferon-β. Fourteen patients were given interferon daily for 4 wk. Interferon receptors per cell decreased to about 50% of baseline but increased to baseline by 2 wk after therapy ended. The activity of 2′,5′-oligoadenylate synthetase rose about fivefold during therapy, decreasing to baseline by 1 wk after the end of therapy. The seven other patients were given interferon daily for 2 wk, no interferon for 2 wk and then interferon daily for 2 wk more. During both periods of therapy on this schedule, interferon receptors decreased to about 50% but returned to baseline 1 wk after the interferon was stopped. The activity of 2′,5′-oligoadenylate synthetase increased about fivefold during both the first and second periods of therapy and decreased to baseline 1 wk after interferon was stopped. Close negative correlation existed between the number of interferon receptors and the 2′,5′-oligoadenylate synthetase activity. The results of interferon therapy could not be predicted by either the numbers of interferon receptors before therapy or by the decrease in this number during therapy. (HEPATOLOGY 1990;12:1261–1265).