Proliferative and phenotypic characteristics of cells in regional lymph nodes that drain burn injury were examined in rats on day 3 postburn, i.e. at the time of maximal spontaneous proliferation and of interleukin-2 and accessory cytokine (IL-1 and IL-6) production. The importance of IL-1 in spontaneous proliferation of draining lymph node cells was demonstrated by stimulation of IL-2-driven proliferation by recombinant IL-1 in vitro and by susceptibility of unstimulated proliferation to anti-IL-1 antibodies, while requirements for IL-6 in draining lymph node cell proliferation were less pronounced. Cell surface phenotyping revealed a slightly increased percentage of CD25+ cells in the blast cell population of freshly isolated draining lymph node cells after injury, which increased further during cultivation. Enrichment in CD8+ cells on day 3 following burn injury was demonstrated, while no changes in total cell population and CD4+ cells was noted. This was however preceded by pronounced percentual decrease of total T cells and CD4+ cells and by increases of B cells and MHC class II+ cells on day 1 postburn. Inhibition of draining lymph node cell proliferation by anti-MHC class II antibodies suggested that this proliferation was class II MHC dependent. The contribution of cell proliferation and/or cell influx to day 3 postburn draining lymph node cell activity is discussed.