The localization of CD95L in different cell types within tumors has not been well defined, and its role in tumor growth is uncertain. In this study, CD95L expression and its contribution to tumor growth are evaluated using genetic polymorphisms and adoptive transfer in genetically deficient mice. CD95L was detected in tumors in vivo at levels up to 10(4)-fold higher than those in cell culture and predominantly in host tumor-infiltrating macrophages, but not in tumor cells. Adoptive transfer into genetically deficient mice revealed that host CD95-CD95L function did not alter tumor growth, demonstrating that CD95L alone does not affect tumor growth.