Because histologically prominent microvascular proliferation is frequently present in glioblastoma multiforme, it has been hypothesized that this neoplasm is particularly dependent on neovascularization for its continued growth and that antiangiogenic therapy might be especially useful. To quantify the histological aspects of microvascular proliferation in glioma, a feasible and reproducible method was developed for computer-assisted image analysis of the visualized microvasculature in glial tissue. This method was used to compare several vascular parameters in histological whole-tumor sections of untreated human glioblastoma multiforme with those in histologically normal cerebral cortex and white matter. There was a significant increase in mean number, area, and perimeter of blood vessels per microscopic field in glioblastoma multiforme compared to normal cerebral white matter. In a substantial number of tumor fields, however, the vascular density was in the same range as that of normal cerebral white matter. The striking heterogeneity of the microvasculature within glioblastoma multiforme was illustrated by the significantly higher standard deviation for the vascular parameters in tumor tissue. The results of this study suggest that many regions of glioblastomas multiforme are not overtly angiogenesis dependent and may be difficult to treat by antiangiogenic therapy alone.