AbstractRecent experiments concerning the possible role of components of the pituitary–adrenocortical axis (ACTH and glucocorticoids) in isolation‐induced intermale fighting behavior in laboratory strains of mice are reviewed. A series of experiments which investigate factors that may influence the successful demonstration of this relationship are described. Differences in performances in standard‐opponent tests of some outbred strains of albino mice are indicated, as well as an interesting positive correlation between the aggressiveness and the relative adrenal weights of the strains employed. Long‐acting preparations of both ACTH and ACTH 4–10, injected throughout a period of isolation, suppressed fighting behavior in intact TO‐strain mice in subsequent standard‐opponent and trained‐fighter tests. After it had been confirmed that vigorous isolation‐induced fighting could be obtained in bilaterally castrated mice which had been subcutaneously implanted with testosterone pellets, the effects of long‐acting preparations of ACTH, ACTH 4–10, ACTH 1–10, and ACTH 4–10 D‐phe on the fighting behavior of such animals were studied. A significant suppression of fighting behavior was evident only with respect to ACTH, suggesting that ACTH 4–10 may have its action on this behavior in a manner rather different from that of the parent molecule. Some evidence was also obtained indicating that the zinc used in the preparation of long‐acting injections of ACTH and its analogs may also cause a decline in the level of fighting behavior, in a standard‐opponent test, in TO‐strain mice which had been castrated and testosterone implanted. While such a finding does not affect the validity of the recorded behavioral influences of ACTH and ACTH 4–10 described earlier, it does seem likely that the presence of this substance in placebo injections would make the demonstration of the actions of the pep tides difficult, as there would be a low level of fighting in all categories. Rather less impressive results were obtained with respect to the influences of ACTH preparations and zinc on castrated—implanted CFW mice.The studies identify a number of the factors which may influence the successful demonstration of a relationship between the functioning of the pituitary—adrenocortical axis and isolation‐induced agonistic behavior in the mouse. A number of general, if tentative, conclusions may also be listed. It seems likely, in spite of the interpretational difficulties caused by what seems to be a complex and rather unstable relationship, that ACTH and glucocorticoids may have profound influences on this type of fighting behavior in this species. One may also conclude that the evidence for an extraadrenal influence of ACTH on this behavior appears stronger as a result of these and related studies and that the actions of ACTH and its analogs on murine fighting behavior may be logically related to the actions of these compounds on the acquisition and extinction of conditioned avoidance reactions in hypophysectomized rats. The possible utility of such actions to the natural territorial habi