The cytokine interleukin-1, IL-1, likely plays an important role in the early stages of atherogenesis. The possible action of probucol and tocopherol on the expression and secretion of IL-1 beta was investigated using the human monocytic leukemia cell line, THP-1. Both probucol and D-alpha-tocopherol inhibit the phorbol ester-induced release of IL-1 beta without altering differentiation. Analysis of IL-1 beta mRNA levels revealed that probucol and tocopherol had an inhibitory effect on the activation of expression of the IL-1 beta gene. The data suggest that the beneficial effects of probucol may be related to inhibition of IL-1 at an early phase of atherosclerotic plaque formation.