The mechanisms responsible for the accumulation of lymphocytes in rejecting allografts may involve lymphokine-mediated changes in blood flow and vascular permeability. Changes in lymphocyte recruitment (LR), regional blood flow (RBF), and vascular permeability (VP) were studied in paired healed subcutaneous urethane sponge grafts inoculated with specifically sensitized lymphocytes (SSL) and allogeneic target cells. Intravenous injection of Indium-111-labeled unsensitized lymphocytes (UL), rubidium-86-chloride, and Iodine-125-labeled albumin was used to assess LR, RBF, and VP, respectively. An increase in LR (p less than 0.001), RBF (p less than 0.001), and VP (p less than 0.001) could be demonstrated at the site of interaction between specifically sensitized lymphocytes and targets bearing the sensitizing alloantigen. Lymphocyte recruitment, blood flow, and vascular permeability indexes were all elevated within 4 hr after graft inoculation, peaked at 8 hr, and declined at approximately the same rate over the subsequent 24 hr. RBF returned to baseline levels by 24 hr, whereas LR and VP remained elevated. Suspension of SSL and targets in dexamethasone acetate (1 x 10(-5) M) before graft inoculation completely inhibited the early increase in RBF, but only incompletely blocked LR and VP. At 24 hr, however, VP was almost totally inhibited and LR remained elevated. These results are consistent with the idea that the interaction between SSL and specific alloantigen in vivo leads to the rapid elaboration of lymphokines, which increases RBF and VP, in addition to the accumulation of circulating unsensitized cells. These vascular effects could partly be responsible for the heterogeneity and nonspecificity of the cellular infiltrate in rejecting allografts. Specific enrichment of the graft infiltrate with sensitized cells would require that other mechanisms be operative.