The kinetics of lymphocyte recirculation in normal and allografted rats with acute cardiac rejection was studied with indium-111 (In-111) labeled splenic lymphocytes in two groups of rats. Group 1 consisted of subgroups of normal Lewis rats infused with In-111 labeled unsensitized syngeneic cells (group 1a); ACI-sensitized syngeneic cells (group 1b); and ACI spleen cells (group 1c). Four rats from each subgroup were killed at 3, 6, 18, and 24 hr after cell infusion for blood, spleen, mesenteric lymph node (MLN), thymus, bone marrow (BM), liver, kidney, muscle, and heart scintillation counts. Group 2 consisted of Lewis recipients of ACI cardiac allografts infused with normal or with ACI-sensitized syngeneic splenic cells. Four rats from each subgroup were killed daily until rejection (day 7) for isotope counts of various organs. In ungrafted rats (group I), splenic accumulation of unsensitized syngeneic cells fell from 50% of the total injected dose/g tissue at 3 hr to 28% at 24 hr, whereas it rose from 12% at 3 hr to 39% at 24 hr in MLN. In contrast, the sensitized syngeneic and allogeneic cells homed preferentially to the spleen with insignificant accumulation in the MLN throughout the experiment. The BM and liver showed moderate accumulation while the thymus and nonlymphoid organs had low concentrations of labeled cells at all times. Splenic accumulation of unsensitized syngeneic cells in allografted rats (group II) showed a steep rise from day 1, reaching a peak at day 3, followed by a plateau--but sensitized cells demonstrated a peak on day 4 followed by a sharp decline until rejection. Accumulation of unsensitized cells in the MLN was significantly higher (P less than 0.001) than that of sensitized cells throughout the study. There was a significant fall (P less than 0.001) in radioactivity of BM, thymus, liver, and nonlymphoid organs from days 1-7, and the cardiac allograft demonstrated a reciprocal sharp rise in radioactivity. There was a significant early accumulation (P less than 0.001) of sensitized cells compared with unsensitized cells in the cardiac allograft on day 1. This study shows that In-111 labeled donor cells bearing surface antigen different from that of the recipient were sequestered from the circulating pool and immobilized in the spleen, but labeled donor cells with similar surface antigen to that of the recipient were recruited into the lymph node lymphocyte recirculating pool. It further demonstrates the difference in migration patterns of normal and sensitized syngeneic cells during acute allograft rejection.