Electrothermocoagulation (ETC) of the individual nuclei of the median region of the hypothalamus (MH) in the C57BL/6 mouse leads to a significant reduction in the cytotoxic activity of natural killer cells (NK) and the number of large granular lymphocytes (LGL) compared with intact or sham-operated controls. This effect, however, is less than that observed after simultaneous destruction of all MH nuclei. By contrast, no significant change in NK activity was noted after ETC of the anterior (AH) or posterior (PH) regions. Diminution of NK activity due to nuclear MH destruction is not an outcome of the change in adenohypophysis secretion provoked by hypothalamic lesion. Natural cytotoxic activity was markedly increased after ETG located either in AH, or MH, or PH. These results indicate that NK- and NC-mediated immunity is governed by a control mechanism situated in the hypothalamus.