Regional lymph node response in F1 hybrid rats in injection of parental adult liver cells was investigated. More than a 10-fold increase in node weight over the uninjected control node was observed on day 11 following injection of 60 X10(6) parental liver cells. The node weight gain was both dose and time dependent although 10 times more liver cells were required than the lymphocyte. Injection of either irradiated (600 rads) or cultured (30 days) liver cells did not reduce the reactivity. The liver cells prepared from 18-day-old fetuses, 70% hepatectomized or portacaval shunted rats were all shown to be reactive, the latter being far superior. This phenomenon is immunological since only parental (semi-allogeneic) but not syngeneic liver cells gave the reaction although a hybrid resistance cannot be denied. Possible mechanisms underlying this phenomenon are discussed.