Monocyte migration within the extravascular space of inflamed tissues is controlled by adhesion molecules and inflammatory cytokines. In this study, we analyzed the capacity of TGF-beta 1 and IFN-gamma to regulate adhesion of human activated monocytes to fibronectin (FN) and to laminin (LM), two components of the extracellular matrix. When cultured in the absence of any of these two stimuli, human monocytes underwent "spontaneous activation" and adhered to both FN and LM. Adhesion to FN was inhibited in the presence of alpha 5 and beta 1 integrin blocking antibodies, whereas beta 2 blocking antibody blocked attachment to LM. Exogenous TGF-beta 1 increased the adhesive ability of monocytes to FN and to LM, respectively, linked to the increase of alpha 5 and beta 2 mRNA and protein synthesis levels. Moreover, an increase in alpha 5 expression at the monocyte cell surface was observed. In contrast, monocytes stimulated with exogenous IFN-gamma lost their capacity to bind to FN and this coincided with the down-regulation of surface alpha 5 expression which occurred at the posttranscriptional level of alpha 5 synthesis. Although IFN-gamma-treated monocytes also showed a decreased ability to adhere to LM, no alteration of beta 2 mRNA levels, beta 2 protein synthesis, and beta 2 cell surface expression was detectable, thus suggesting a modification of the functional state of surface beta 2 integrins. Furthermore, when stimulated with TGF-beta 1, IFN-gamma-pretreated monocytes reacquired the ability to bind to FN and LM. Conversely, IFN-gamma reduced adhesiveness to FN and LM of monocytes initially stimulated with TGF-beta 1. These in vitro adhesive-deadhesive responses of monocytes to TGF-beta 1 and IFN-gamma modulation may reflect mononuclear phagocyte motility within sites of inflammation.