Injection of sheep red blood cells (SRBC) as an antigenic stimulus, causes significant increases (up to 300%) in multiunit neural activity in the preoptic area/anterior hypothalamus of conscious rats. This increase occurs on the fifth or sixth day after immunization, at the time of first appearance of circulating antibodies at a serum titer of 1:32, increasing to 1:128 by day 10 following sensitization. Treatment with the immunosuppressive drug cyclophoshamide was able to prevent both antibody production and the expected increases in electrical activity in 5 of 6 rats; the one remaining animal showed a low level of circulating anti-SRBC antibodies on day 10 (1:32) and also, a small increase (36%) in neural activity at the expected time. These results provide further evidence that activation of the immune system is able to alter neuronal activity in an area of the brain important in the regulation of both neuroendocrine and neuroimmunomodulatory mechanisms, and that such activity is probably due to soluble secretory products released from components of the immune system.