Because of the crucial role played by tumor neovascularization in contrast enhancement, we studied the CT imaging findings in a transplantable rabbit brain tumor, the VX2 carcinoma that induces angiogenesis and the breakdown of blood-brain barrier associated with contrast enhancement. Tumor detection by contrast enhancement followed the peak of angiogenesis. Inhibition of angiogenesis, by copper depletion and penicillamine, led to avascular tumors that lack contrast enhancement. Furthermore, there was no contrast enhancement in brain adjacent to the tumor of normocupremic rabbits or within the hypocupremic tumor, despite the breakdown of the blood-brain barrier, without the concomitant presence of angiogenesis. We conclude that contrast enhancement of intracranial tumors is dependent primarily on the proliferation of the microvasculature.