To determine histological correlates of the variability of glucose consumption in astrocytomas, the authors performed positron emission tomography (PET) with 18F-2-fluoro-2-deoxy-D-glucose (FDG) and matched the PET scans three-dimensionally with computerized tomography scans obtained in a stereotactic frame before biopsy. Ten patients with astrocytomas of World Health Organization Grade 2 or 3 were studied; patients with glioblastomas, oligodendrogliomas, or oligoastrocytomas were excluded from the study to avoid any confounding effects of different cell types and necroses. In samples of pure tumor, glucose consumption correlated significantly with cell density, but not with nuclear polymorphism. It is concluded that tumor cell density is a major determinant of glucose consumption in astrocytomas. The use of PET with FDG may help to locate the highest cell density and thus improve the diagnostic yield of stereotactic biopsy.