The primed lymphocyte typing (PLT) test is based on the observation that lymphocytes from HLA-D-region incompatible individuals, when cultured together in vitro, undergo blast transformation and, after clonal expansion, they revert to small lymphocytes and give an accelerated response when restimulated by the same stimulator cells. The PLT test is carried out by culturing responder and irradiated stimulator cells in a primary mixed lymphocyte culture for 10 d. Anti-HLA-DP PLT reagents are normally obtained by culturing peripheral blood lymphocytes from HLA-A, -B, -C, -DR, and -DQ compatible individuals in order to avoid the expansion of clones to other stimulating determinants. The relative importance of the amino acid differences seems also to be determined by the DR haplotype of the responder population since T cell stimulation induced by HLA-DP incompatibilities associated with the presence of DR3 in the responder population is higher than those induced in other haplotypes.