Both cell proliferation and cell death occur simultaneously in tumor tissue, and extent of tumor growth reflects the net balance of these events. We correlated cell proliferation, spontaneous cell death, and alterations in tumor suppressor proteins with one another and with survival of patients with primary astrocytic tumors. In 39 astrocytic tumor specimens (6 pilocytic astrocytomas, 14 fibrillary astrocytomas, 9 anaplastic astrocytomas, and 10 glioblastomas), we determined the MIB-1 labeling index, the apoptotic ratio according to nick end labeling with morphologic confirmation, the p53 labeling index, and the presence of p53 or PTEN mutations. MIB- I labeling indices of pilocytic astrocytomas, fibrillary astrocytomas, anaplastic astrocytomas, and glioblastomas were 0.30+/-0.32; 1.84+/-1.87; 19.3+/-6.42; and 28.0+/-14.5 (mean +/- SD), respectively. Corresponding apoptotic ratios were 17.9+/-5.16; 3.96+/-3.57; 1.18+/-0.93; and 2.11+/-1.60 (mean +/- SD). The apoptotic ratio in pilocytic astrocytomas was significantly higher than in other astrocytic tumors (fibrillary astrocytomas, p < 0.05; anaplastic astrocytomas and glioblastomas, p < 0.01). MIB-1 showed a significant negative correlation with apoptosis (p < 0.01). MIB- I and apoptosis showed significant negative and positive correlations with patient survival (p < 0.01). Mutations of p53 and PTEN show no correlation with survival and apoptotic ratio. The apoptotic ratio can clearly distinguish pilocytic astrocytomas from other tumors, and this biological feature may reflect less aggressive growth of pilocytic astrocytomas.