Vascular endothelial growth factor (VEGF) is a specific mitogen for endothelial cells. We studied the production of VEGF by human umbilical vein endothelial cells (HUVEC) and smooth muscle cells (SMC) in response to the stimulation with interleukin-1alpha (IL-1alpha). HUVEC expressed VEGF mRNA in response to IL-1alpha in dose- and time-dependent manners. In HUVEC VEGF protein was detected only in cell lysates whereas in SMC most of the VEGF protein was detected in the conditioned medium. Immunofluorescent staining also confirmed the cell-associated VEGF in HUVEC. IL-1alpha also induced the expression of mRNA for IL-1alpha itself in HUVEC. Cycloheximide treatment of HUVEC slightly inhibited the IL-1alpha-induced expression of VEGF mRNA, and IL-1alpha may mediate, at least in part, VEGF expression in response to IL-1alpha. The growth of HUVEC stimulated with IL-1alpha was inhibited by a neutralizing antibody against VEGF. We conclude that IL-1alpha and VEGF may play an important role in autocrine growth regulation of HUVEC.