When highly purified neonatal rat islet tissue, derived after 10 days in vitro, was allografted, it was found to be nonimmunogenic or weakly immunogenic. In contrast, nonislet pancreatic components, derived from the same culture system, transplanted with highly purified islet tissue resulted in rejection in 88% of cases. Extension of the culture period did not result in reduced immunogenicity of the nonislet material. Immunostaining of islet or nonislet tissue from the culture system failed to demonstrate major histocompatibility complex (MHC) class II positive cells in the islet tissue, whereas the presence of MHC class II staining cells in the nonislet components was clearly demonstrable. These results demonstrate that the islet tissue obtained by culture isolation is free of cells capable of stimulating an allogeneic immune response and are consistent with the hypothesis that the absence of MHC class II positive antigen-presenting cells reduces the immunogenicity of the tissue and enhances the survival of allogeneic grafts.