Behavioral effects of murine interferon-alpha and -gamma were explored using a well-characterized system for detecting interferon effects. In addition, the effectiveness of human interferon-alpha was determined. Mouse gamma-interferon decreased activity and food-related behavior, effects that were similar to the effects of mouse alpha-interferon. Equivalent doses of the human preparation had little effect upon these measures in mice. Some common action of alpha- and gamma-interferon is likely responsible for the similar effects seen for the two molecules. Low effectiveness of the human preparation in mice was predicted due to the differences in receptors between species.