Cell to cell interaction is one of the key processes effecting angiogenesis and endothelial cell function. There are many factors which can mediate this interaction including Wnt-signaling-related molecules. Wnt signaling is involved in many developmental processes and cellular functions. There is increasing evidence suggesting that Wnt signaling has a role in regulating endothelial cell growth although the precise mechanism is unclear. In this study, we established a coculture system to examine how Wnt-1 signaling regulates human umbilical vein endothelial cell (HUVEC) growth and behavior. We found that Wnt-1 signals inhibited BrdU incorporation in HUVECs and the number of labeled cells also decreased in proportion to the number of Wnt-1-expressing cells present (P < 0.05). Moreover, HUVECs cocultured with Wnt-1-expressing C57MG cells clumped together rather than remaining scattered throughout the culture. These effects were dependent on cell contact. Treatment of HUVEC with LiCl, which inhibits the activity of GSK-3beta and mimicked Wnt-1 signaling, also inhibited the BrdU incorporation in endothelial cells. Our results suggest that Wnt signaling has a role in endothelial cell growth control and this is mediated through cell-cell contact. They also suggest that Wnt signaling might participate in angiogenesis by regulating endothelial cell growth and function.