The effects of 3 h lasting local hyperthermia on immune cell traffic through the normal human skin to afferent lymphatics, cell phenotypes, responsiveness, and stimulatory properties were studied in eight men. Cells were harvested from lymph drained from foot skin. Heating the skin in a water bath of 44ยฐC (skin temperature 2 mm under the surface 39ยฐC) evoked an augmented traffic of mononuclear cells to lymph with preponderance of large, macrophage-like, Ia-positive cells, among them Langerhans cells. Lymphocytes obtained from the heated skin lymph revealed in culture increased spontaneous blastic transformation rate, augmented responsiveness to phytohemagglutinin (PHA), and enhanced PHA-presenting properties to autologous peripheral blood mononuclear (PBM) cells. An increased stimulatory activity on allogeneic mixed lymphocyte reaction (MLR) was also observed. Lymph from heated skin augmented the PBM responsiveness to PHA and showed increased interleukin-1 -like activity. Local heating of the skin is a potent signal initiating augmented traffic, and enhanced responsiveness and stimulatory activity of "passenger" immune cells. Their rapid nonspecific activation makes them indiscriminately active against a wide range of antigens before the specific response is developed.