Previous studies have demonstrated an infiltration of monocytes and increased levels of IL‐1β and TNF‐α in some chronic inflammatory tissues. Interleukin‐1β and TNF‐α are capable of protecting monocytes from spontaneous apoptosis and thus maintain their viability in vitro. To study the possible effects of these cytokines on the differentiation and function of recruited monocytes, a model has been developed in which monocytes isolated from human peripheral blood were differentiated into macrophages in serum in the presence or absence of IL‐1β or TNF‐α. Monocytes cultured with IL‐1β and TNF‐α underwent substantial changes in morphology, similar to those observed in monocytes undergoing differentiation into macrophages. The cultured cells increased in size and vacuolization and their content of acid phosphates increased 10‐fold. Although they exhibited the morphological characteristics of macrophages, monocytes matured in the cytokines differed functionally from those cultured in serum in a lower expression of HLA‐DR, lower ability for triggering the proliferation of allogeneic lymphocytes, higher expression of mannose receptor and greater production of superoxide and TNF‐α. This data suggests that IL‐1β and TNF‐α direct monocyte differentiation into macrophages with a reduced antigen‐presenting and an increased pro‐inflammatory factor‐releasing phenotype. Elevated levels of IL‐1β and TNF‐α in the inflammatory tissues may therefore not only prolong the survival of recruited monocytes, but maintain them in an inflammatory state.