The biological functions of macrophage-inflammatory protein 1alpha (MIP-1alpha) include the regulation of inflammatory processes and the inhibition of early hematopoiesis. We investigated the regulation of MIP-1alpha in various cell types in response to IFN-alpha and IL-4 by mRNA analysis and examination of MIP-1alpha protein levels in culture supernatants. In peripheral blood mononuclear cells (PBMNCs) and purified monocytes, IFN-alpha induced MIP-1alpha mRNA expression and stimulated MIP-1alpha secretion in LPS-activated monocytes to almost twice the value observed with LPS alone, whereas IL-4 caused a reduction by 80-95%. The stimulatory effect of IFN-alpha on MIP-1alpha production appeared to be dominant over its inhibition by IL-4. This effect was most pronounced after prolonged incubation periods. In fibroblasts obtained from human foreskin, IFN-alpha in combination with IL-1 stimulated MIP-1alpha secretion to more than three times the level obtained with IL-1. Stimulation of MIP-1alpha expression by IFN-alpha may indirectly influence inflammatory processes and the regulation of early hematopoiesis.