C5a anaphylatoxin injected via implanted cannulae into the perifornical region of the hypothalamus stimulated eating in sated rats. C5a also attenuated carbamyl choline-induced drinking, and carbamyl choline inhibited C5a-induced eating, a mutual inhibition characteristic of the adrenergic-cholinergic interactions at this site. The increased food intake induced by C5a was also reversed by phentolamine, an alpha-adrenergic antagonist. Granulocytes infiltrating as a result of C5a-mediated leukotaxis did not arrive at the site in time to influence C5a activity. We propose that C5a in some way activates an alpha-adrenergic receptor system in the hypothalamus, and that anaphylatoxins could mediate neuropsychiatric symptoms sometimes associated with immune complex diseases affecting the central nervous system.