Changes in distal angiogenesis in response to irradiation of primary tumors are not known. To this end, PC-3, a human prostate carcinoma, and FSA-II, a murine fibrosarcoma, were grown in the gastrocnemius muscles of male nude mice. Distal angiogenesis was measured in gel containing human recombinant basic fibroblast growth factor placed in the cranial windows of these mice. PC-3-bearing mice showed inhibition of distal angiogenesis, as compared with non-tumor-bearing controls. Surgical removal of tumors tended to accelerate distal angiogenesis; in comparison, after irradiation of the PC-3 primary tumor, rates of angiogenesis in the cranial window were retarded. Irradiation of the non-tumor-bearing leg or of non-tumor-bearing animals showed no measurable effect on rate of growth of vessels in the cranial window. Similar results were found with the FSA-II tumors, with slowed distal angiogenesis in tumor-bearing animals and further suppression in animals with irradiated tumors. These results demonstrate that the effect of irradiation of a primary tumor on angiogenesis at a distal site may differ from the effect of surgical removal of the primary tumor. Unlike surgery, irradiation of a tumor may enhance angiogenic suppression at a distal site, and this difference may involve host-tumor interaction.