Properdin is the only known positive regulator of the alternative pathway of complement activation. Northern blot analysis of cell lines derived from fibroblasts, B‐cells, hepatoma cells, and cells of the monocyte‐macrophage lineage revealed properdin expression only in the myelomonocytic cell line HL‐60, in the monoblastic cell line U‐937 and in the monocytic line Mono Mac 6. Culture of Mono Mac 6 cells for 24 h with phorbol 12‐myristate 13‐acetate, bacterial lipopolysaccharide and the cytokines interleukin‐1β and tumour necrosis factor‐α enhanced mRNA abundance, with the strongest effect (tenfold) being observed with the lipopolysaccharide. In contrast, recombinant interferon‐γ consistently halved properdin mRNA abundance. The same pattern was found for the secretion of properdin as detected by ELISA of Mono Mac 6 supernatants. The suppressive effect of interferon‐γ on properdin mRNA abundance was also demonstrated for primary blood monocytes. The data suggest that the expression and secretion of this complement regulatory protein by monocytes is differentially regulated by cytokines and link the immune response with alternative pathway activation.