We have proposed a hypothesis in which vascular endothelial cells, rather than or in addition to bone-marrow-derived cells, play an integral part in the antigen presentation event of cell-mediated immune phenomena including delayed-type hypersensitivity (DTH). Previously we have shown that a DTH ear-swelling response can be adoptively transferred in rats, using as few as 2 x 10(7) in vitro conditioned immune spleen cells. The transfer is antigen-specific, requiring the same sensitizing antigen in both the in vitro conditioning step and in the ear-test challenge. Adoptive transfer is also genetically restricted by alleles of the RT-1 region of the rat, requiring histocompatibility between immune donor cells and the naive recipient. In additional experiments, F1 to parental bone-marrow chimaeras were constructed such that the bone-marrow-derived cells and the non-bone-marrow-derived cells were of different RT-1 allotypes. When these chimaeras were used as adoptive transfer recipients, the transfer of DTH was possible only if the immune donor cells and the recipient non-bone-marrow-derived cells shared a common RT-1 haplotype, regardless of a shared haplotype with the bone-marrow-derived cells. These results point to a critical role for non-bone-marrow-derived cells (endothelial cells) in the DTH inflammatory response.