The vast majority of T cells present in chronic inflammatory lesions are of the helper-inducer/memory (CD45RO+CD29+) phenotype; suppressor-inducer/naive cells (CD45RA+) are virtually absent. Furthermore, CD4+ T cells are found more frequently than CD8+ cells. Previous in vitro studies have suggested that this may be, in part, due to the increased capacity of CD45RO+CD29+ T cells to bind to endothelium and, thus, enter inflammatory foci but no in vivo evidence for preferential migration exists. To investigate this, suction blisters were generated over a purified protein derivative of tuberculin-induced delayed-type hypersensitivity lesions in humans and the phenotype of the blister cells was studied. At all time points, a preponderance of CD45RO+CD29+ cells over CD45RA+ cells and of CD4 over CD8 cells was demonstrated. Because of the rapid kinetics, this appears to represent preferential migration of these cell types rather than in situ proliferation or phenotype conversion. In addition the expression of the CD45RO but not the CD45RA antigen was up-regulated on blister T cells compared to blood T cells. Analysis of blister fluid showed high concentrations of interleukin 6 but not tumor necrosis factor-α or lymphotoxin. This study shows for the first time directly in vivo that CD45RO+ T cells migrate preferentially into inflammatory lesions. Furthermore, it illustrates the potential usefulness of this system in the analysis of the early phases of the immune inflammatory response.