Intravenous injections of physiologic doses of cortisol resulted in both hematologic and immunologic changes in channel catfish peripheral blood leucocytes. These changes mimicked those seen when catfish were acutely stressed by handling and transport. 2. Eighteen hours after the administration of cortisol, decreases in the number of circulating lymphocytes and concomitant increases in the number of circulating neutrophils were observed, i.e. to the same levels seen previously in stressed fish. 3. Functional analysis of peripheral blood leucocytes from cortisol-injected fish indicated that the remaining lymphocytes were no longer capable of responding to mitogenic stimuli. 4. This suppression of mitogenic stimuli was not seen when peripheral blood leucocytes were cultured in vitro with physiologic doses of cortisol. 5. This latter observation suggests that the cortisol alone was probably not directly responsible for the loss of responsiveness but possibly acted in vivo as an initiator of other events that eventually resulted in the observed immunosuppression.