Idiopathic pneumonia syndrome (IPS) is a significant cause of morbidity and mortality post-BMT in humans. In our murine IPS model, lethal pre-BMT conditioning and allogeneic T cells result in the recruitment of host antigen-presenting cells (APC) into the lung by day 3 and then donor T cells by day 7 post-BMT concomitant with development of severe lung dysfunction. CCL2 induction was found in bronchoalveolar lavage fluid (BALF) of these recipients prior to host monocyte influx. The major receptor for CCL2 is CCR2 present on monocytes and this interaction has been shown to play a crucial role in monocyte recruitment in inflammation. To determine whether blockade of the CCL2/CCR2 recruitment pathway could hinder host monocyte influx, lethally conditioned wild type (WT), CCL2^-/- or CCR2^-/- recipients were transplanted with allogeneic marrow and spleen cells. WT and ^-/- recipients exhibited equivalent lung dysfunction early post-BMT. The frequencies of host macrophages as well as donor CD4⁺ and CD8⁺ T cells in the lungs post-BMT did not differ between WT and ^-/- recipients. However, the T cell-dependency of the host CD11b⁺MHC class II⁺ (monocytes/macrophage or dendritic) cell influx was lost in CCR2^-/- recipients. In CCR2^-/- mice, this influx was accompanied by elevated levels of CCL20 whose exclusive receptor is CCR6 found on myeloid dendritic cells. Post-BMT BALF and sera of CCL2^-/- and CCR2^-/- mice did not reveal any decrease in Th1 or Th2 cytokines or chemokines compared to WT mice. CCL2^-/- mice had a deficiency of CCL2 in their BALF and serum post-BMT, as expected, confirming our hypothesis that CCL2 is predominantly host-derived. Our data indicate that IPS can occur independently of host expression of CCL2 or CCR2 and suggest that compensatory mechanisms exist for regulating APC recruitment into the lung during the early post-BMT period.