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The degradation products of hyaluronan are known to stimulate endothelial‐cell proliferation and to promote neovascularization associated with angiogenesis, whilst native high‐molecular‐weight hyaluronan is inhibitory to these processes. To investigate the cellular signalling pathways coupled to hyaluronan‐induced responses in angiogenesis, we have analyzed early‐response gene expression in vitro, in cultured bovine aortic endothelial cells. Angiogenic oligosaccharides of hyaluronan induced rapid transient up‐regulation of the immediate early genes c‐fos, c‐jun, jun‐B, Krox‐20 and Krox‐24. In contrast, native hyaluronan when used alone failed to elicit a significant change in expression of any of the genes tested, and when used in combination with angiogenic oligosaccharides of hyaluronan, gave a dose‐dependent inhibition of induced gene expression. However, prior addition of angiogenic …