In order to examine possible neurophysiological changes during an immune response, we have recorded neural activity in a conscious animal bearing chronic recording electrodes in the preoptic area/anterior hypothalamus (PO/AH) and hypothalamic paraventricular nucleus (PVN). Male rats were sensitized with sheep red blood cells (SRBC) injected intraperitoneally. Basal PO/AH multiunit activity (MUA) was recorded as 14.7 +/- 2.1 Hz prior to sensitization and was seen to increase significantly to a maximum of 33.1 +/- 6.0 Hz (p less than 0.005) five days after SRBC injection. This increase correlated with the initial appearance of anti-SRBC serum antibodies at a mean antibody titer of 1:32. Also recorded were decreases in PO/AH MUA on days 3 and 8 after the sensitization (8.2 +/- 2.4 Hz, p less than 0.005); 7.1 +/- 3.3 Hz, p less than 0.005, respectively). Basal PVN MUA was recorded as 14.7 +/- 2.4 Hz. It decreased significantly for the first three days after immunization, and then returned to a basal rate before increasing to 25.9 +/- 8.4 Hz (p less than 0.005) on day 6. On the ninth and tenth days after SRBC injection PO/AH and PVN MUA levels returned to those recorded before immunization.