Products of leukocytes were found to activate cultures of keratocytes, manifested by the increased incorporation of thymidine or leucine. The keratocyte activation capacity crosses the species barriers between rabbit, monkey, and human. The level of secreted keratocyte-activating factor(s) (KAF) depends on the stimulation of the leukocytes. Thus unstimulated rabbit leukocytes produced very little or no KAF, whereas significant levels were produced by leukocytes stimulated with lipopolysaccharide (LPS) or concanavalin A. High levels of KAF were also found in supernatants of human mononuclear leukocytes stimulated by LPS. The effects of the activated leukocyte supernatants on keratocyte metabolism resembled the increased metabolic activity induced by the fibroblast and epidermal growth factors. The relationship between KAF and a possible modulating role of the products of lymphoid cells on corneal wound healing is suggested.