A prospective study performed in unrelated, unimmunized rhesus monkeys revealed that serological matching for D-associated Ia1 antigens improves kidney allograft prognosis, provided that the recipients are nonreactive in mixed lymphocyte cultures (MLC) against their donors. MLC-negative host-donor combinations showed a more than 3-fold increase in the mean survival time as compared with MLC-positive combinations. Apparently, compatibility for the most important MLC-stimulating determinants is required for a significant improvement in graft survival. On the other hand, matching for A and B loci antigens did not play a decisive role. Since the relatively simple matching on the basis of identity for Ia1 (or DR) antigens yields a rather high proportion of MLC-nonreactive combinations, this method is likely to become an essential addition to the conventional matching procedures, also in clinical organ transplantation.