The in vitro binding of 125I-labelled human alpha-interferon to peripheral blood mononuclear cells from 13 patients with chronic hepatitis B during interferon therapy was assayed in order to identify changes in the number of interferon receptors during treatment. Nine patients were treated with human alpha-interferon (Hu alpha-IFN) or human beta-interferon (Hu beta-IFN) daily for 4 weeks. During therapy, receptor sites per cell decreased by 40%. Two weeks after therapy ceased, this number had returned to the pretreatment level. The other four patients were given Hu alpha-IFN daily for 2 weeks, no injections for 2 weeks, and daily injections for 2 weeks. During both periods of therapy, receptor sites decreased by 40%. The number increased to 94% of the pretreatment level 1 week after the first period and to 101% 2 weeks later. It was 80% 1 week after the second period of injections and 108% 2 weeks later.