To determine the role of the pleiotropic cytokine interleukin-1 (IL-1) on the activation of endothelial cells during inflammation and angiogenesis, pure populations of human dermal microvascular endothelial cells (HDMEC) were obtained by immunoaffinity purification using Ulex europaeus agglutinin-1 and platelet endothelial cell adhesion molecule-1 (PECAM-1) antibody. Exposure of HDMEC to IL-1beta induced morphologic and physiologic changes characterized by 1) phenotypic modulation of endothelial cells from epithelioid to spindle-shaped cells accompanied by reorganization of vimentin filaments; 2) gradual decrease to a complete absence of the endothelial cell markers von Willebrand factor (vWf) and PECAM-1; and 3) increased capability to form tubule-like structures when overlaid with collagen gels. The IL-1 effect on cell morphology, growth, and decrease of endothelial cell antigens was potentiated by basic fibroblast growth factor (bFGF). Similar results were observed in mitotically arrested gamma-irradiated cells demonstrating that the spindle-shaped cells observed after IL-1 stimulation were derived from epithelioid endothelial cells and that DNA synthesis was not required to effect these changes. Immunostaining with an antibody specific for human fibroblasts was negative and further confirmed the endothelial cell origin of the spindle-shaped cells. These data demonstrate that IL-1 can induce phenotypic changes in HDMEC from epithelioid to spindle-shaped, mesenchymal-like cells, that these cells are more susceptible to stimulation by bFGF, and that they lose biochemical and functional properties characteristic of epithelioid HDMEC.