Bilateral symmetrical electrolytic lesions were produced in the following areas of the rat brain: hypothalamus, reticular formation, thalamus, superior colliculus, caudate nucleus and amygdaloid complex. Brain-lesioned and control sham-lesioned animals were immunized 24 h after operation with bovine serum albumin, and examined for antibody production, Arthus reactivity and delayed skin hypersensitivity 10, 20 and 30 days after sensitization. The intensity of Arthus and delayed skin reactions, and the rate of circulating antibody formation were significantly reduced only in hypothalamus-lesioned and reticular formation-lesioned rats. This study provides strong evidence for a relationship between the activity of some brain structures and the function of the immune system. It has been postulated that neural, endocrine, lymphatic and non-lymphatic components cooperate in the lymphatic microenvironment and constitute true functional units of the immune potential. Taking into account neuro-endocrine and lympho-endocrine communications and relations, three possible explanations were proposed for the changes in immunological responses which might be accomplished by electrolytic damage of hypothalamic and reticular formation areas of the rat brain.