Macrophages and T cells have a pivotal role in orchestrating the acute lung allograft rejection response. We investigated the spatial and temporal distribution of these immune cells and the synthesis patterns of the T(h)1- and T(h)2-cytokine IL-12 and IL-10 during the early course after transplantation (Tx). Orthotopic single-lung Tx was performed in Lewis to Lewis (syngrafts) and Brown Norway/Lewis F(1) hybrid to Lewis (allografts). Naïve lungs, syngrafts after 5 days and allografts after 3 and 5 days were analyzed for CD68(+), CD163(+) and CD3(+) cells by immunohistochemistry and IL-12 and IL-10 were detected by immunofluorescence. CD68(+) macrophages increased in number after allogeneic Tx compared to syngeneic Tx on day 5 (P<.001), CD163(+) macrophages sequestrated early around veins (day 3) compared to the accumulation around arteries and bronchioles (P<.001) while CD3(+) T cells were scarce. There was a predominance of IL-12 over IL-10 on day 5 after allogeneic Tx (P<.001). CD68(+) macrophages were the most abundant cells during acute pulmonary rejection and CD163(+) macrophages showed a characteristic distribution pattern over time around vessels and bronchioles. The up-regulation of IL-12 reflects an early response after allo-antigen exposure, indicating a strong impact of the initiation of the T(h)1 pathway at an early phase during acute lung rejection.