To evaluate the relation between hypervascularization and vascular endothelial growth factor (VEGF) in the thyroid glands of patients with Graves disease, 19 Graves disease tissues and 6 normal thyroid tissues were studied by immunohistochemistry, in situ hybridization (ISH), and reverse transcriptase-polymerase chain reaction. The mean microvascular densities per follicle and per millimeter of the thyroid follicles' circumferential length in the Graves disease tissues (mean 3.37 and 13.91) were significantly higher than those in the normal thyroid tissues (mean 2.15 and 7.28) (tied P = .0005, P = .0185, and P < .05, respectively). An antibody against VEGF markedly reacted with hyperplastic follicular cells in Graves disease. The intensity was especially strong in the cells covering papillary growth regions containing accumulated microvessels. By ISH, VEGF messenger RNA (mRNA) signals were also detected in the hyperplastic follicular cells in Graves disease tissues and were especially strong in papillary growth regions. The VEGF receptor-1 (Flt-1) protein and mRNA were observed in endothelial cells of all Graves disease tissues. These findings suggest that hypervascularity in Graves disease tissues is related to upregulated VEGF expression in hyperplastic follicles.