Lymphocyte infiltration of heart grafts was monitored using pulses of 111In-labeled syngeneic lymphocytes. The cells were injected into cyclosporine (CSA)-treated or untreated rats that had received an allograft 1, 2, 4, 6 and 8 days previously. Accumulation of the labeled cells in the graft was measured 24 h after injection, and was compared with that in the animal''s own heart. For the 1st 3 days after grafting, 111In-labeled lymphocytes accumulated to the same extent in the grafts of untreated and CSA-treated rats. However, the substantial rapid increase in lymphocyte accumulation in the graft that occurs in the untreated recipient between days 4 and 5 did not occur in CSA-treated recipients. From day 5-day 9 the accumulation of labeled cells in CSA-maintained grafts was not greater than in syngeneic nonrejecting grafts; it was significantly less than in the untreated rejecting grafts. At early times after grafting, removal from the labeled cell population of lymphocytes with reactivity against the histocompatibility antigens of the graft resulted in a reduction in the extent to which these lymphocytes accumulated in the graft.