Peripheral mononuclear cells from 29 patients with liver disease and from 15 normal subjects were examined for cellular sensitivity to purified bovine type I and type II collagens by the in vitro production of leucocyte migration inhibitory factor. Mononuclear cells from 21 (69%) of the patients responded to type I collagen, but cells from only one (3%) did to type II collagen. In normal subjects, there were no response to both collagens. As compared with the corresponding humoral antibody response, the cellular sensitivity was more specific for type I collagen in patients with liver disease. These data demonstrate that cellular sensitivity to type I collagen exists in liver disease, presumably in relation to hepatic fibrosis.