The effects of retinol (vitamin A alcohol), retinoic acid (vitamin A acid), and beta-carotene (pro-vitamin A) on human interferon (HuIFN) action were examined in vitro. Retinoic acid and beta-carotene, at concentrations in or near the physiologic range, were consistently found to behave as oppositional signals in relation to HuIFN alpha and beta. Thus retinoic acid (and retinol) inhibited the stimulatory action of interferon (IFN) on monocyte membrane function, and this inhibition was reversed by beta-carotene; beta-carotene alone modestly potentiated IFN in this system. Remarkably, for the inhibitory action of IFN on lymphoblastoid cell division, the converse was true: beta-Carotene inhibited the cytostatic action of IFN, and this inhibition was reversed by retinoic acid; retinoic acid alone modestly potentiated IFN in this system. These initial observations suggest a regulatory mechanism whereby beta-carotene potentiates the stimulatory effects but inhibits the suppressive effects of HuIFN on host effector cells. Their significance is discussed with reference to the putative anticancer role of dietary beta-carotene.