Retinoic acid (RA) is a well-known immunological modulator. Although it has been shown that RA stimulates IL-1 expression in monocytes, it is of interest for understanding of the regulatory role of RA in inflammation to examine whether RA also modulates the expression of the IL-1 receptor antagonist (IL-1ra), which is reported to reduce IL-1 beta-mediated inflammation. In this study, we examined the effect of RA on expression of IL-1 beta and IL-ra in phorbol-myristate-acetate (PMA)-activated human monocytes. RA enhanced gene expression and production of IL-1 beta in PMA-activated monocytes. However, interestingly, gene expression and production of IL-1ra in the cells were markedly inhibited by RA. These results show that RA differentially regulates IL-1 beta and IL-ra expression in PMA-activated human monocytes and suggest that RA may promote IL-1-mediated inflammation.