In 26 patients the vascular morphology of pretreatment biopsies from oral squamous cell carcinomas (scc) was studied. Patients had been treated by radiation alone and followed up for 25-73 months. Vascular endothelial cells were identified using antifactor VIII staining. The distances from 700 randomly selected tumor cells to the closet blood vessel were measured in each tumor. Stepwise logistic regression analysis revealed that tumors with fewer than 21% of the morphologically intact tumour cells located within 48 microns of the closest blood vessel had a better control rate than tumors with a higher proportion of tumor cells within this distance. Using the analysis as a predictive assay, local tumor control was predicted from a single histological section with a sensitivity of 81% and a specificity of 60%. In correctly predicted cases of local control, the average median distance between tumor cells and blood vessels was 105 microns. These tumors formed well differentiated avascular tumor cell nests that were surrounded by stroma and blood vessels. Mitotic figures were observed only in the outer rim of cell nests while the center was often keratinizing or necrotic. In cases of correctly predicted treatment failures the average median distance from intact tumour cells to capillaries was 76 microns. These tumors showed varying degrees of organization and capillaries penetrating tumor cell areas. Clinical outcome of radiation therapy of oral scc appears to be correlated with different patterns of tumor architecture and blood supply.