We studied the relation of hypoxia-inducible factor-1alpha (HIF-1alpha) to vascular endothelial growth factor and vasoactive factors during the healing of gastric ulcers. The gastric ulcers were divided into three stages (active stage, healing stage and scar stage). The expression of HIF-1alpha, endothelin-1, inducible nitric oxide synthase, and vascular endothelial growth factor mRNA was highest during the active stage of ulcer healing, and endothelin-1, vascular endothelial growth factor protein levels and nitric oxide were higher during the healing stage. Thus, levels of HIF-1alpha mRNA tend to increase during the active stage of gastric ulcer healing, suggesting that this factor participates in the induction of endothelin-1, inducible nitric oxide synthase, and vascular endothelial growth factor. Also, the HIF-1alpha mRNA level did not differ significantly among the various stages of ulcer healing, and detectable levels of HIF-1alpha protein were not found during any stage. This suggests that these angiogenic factors and vasoactive substances may be induced by HIF-1alpha. During the active stage on endoscopic examination, considered the initial phase of ulcer healing, the process of ulcer healing has begun, and the tissue at the ulcer margin has already been reoxygenated.