T cells expressing CD4 can be farther subdivided by their expression of CD45R In humans, CD45RO+ cells function as memory T cells, and CD4+CD45RA+ function as naive T cells, i.e., cells that have never previously encountered antigen. In the rat, similar functional division of CD4 cells can be made with antibody OX-22 (anti-CD45RC) with CD4+CD45RC- and CD4+CD45RC+ identifying the memory and naive phenotypes respectively. With use of the rat model, we studied the effect of burn injury on CD4 cell subpopulations and memory and naive T cells in lymph nodes draining the burn wound (NDB) and spleen. In the NDB we found that numbers of memory and naive CD4 cells increased significantly as a function of time after burn injury, and that this increase was greater for naive cells (5.7-fold) than for memory cells (4.1-fold). However, in the spleen, we found memory T-cell numbers decreased significantly on postburn days 12 and 18, whereas naive CD4 cells in the spleen manifested no changes at any time after burn. These results may be explained by the different trafficking patterns of memory and naive cells. Based on the cell surface marker, L-selectin, naive cells preferentially migrate into the NDB where they undergo differentiation into memory cells. Memory cells selectively migrate into inflamed burned tissue, which may account for their lesser-fold increase in NDB when compared to naive cells, and their decreased numbers in the spleen after burn injury.