Crossmatch tests of the prospective kidney-transplant donor's lymphocytes with the serum of the prospective recipient in 225 transplants showed that eight of 195 with negative crossmatch failed to function immediately, in contrast to 24 of 30 with positive crossmatch (p less than 0.001). Immediate failure occurred in significantly higher numbers among patients with a higher risk of having antibodies, such as multiparous females and patients receiving secondary transplants. The effect was not a nonspecific one, for more immediate failures occurred among transplants from unrelated than among those from related donors. The corresponding frequency of positive crossmatch was also lower among related donors. The presence of preformed cytotoxic antibodies against the donor appears to be a strong contraindication for transplantation.