Electrical stimulation of the anterior hypothalamus in cats elicits a behavior called restlessness. When a switch is available for the cats to shut off the electrical stimulation, the cats learn to turn off the stimulation (switch-off response; SOR). In this study, we examined the relationship between the SOR and immunoendocrinological alterations. First of all, an escapable stimulation, in which cats could turn off the stimulation, was applied (escapable condition; EC). One month later, inescapable stimulation was delivered under the same conditions except for the fact that the cats could not turn off the stimulation (inescapable condition; IC). A behavioral analysis revealed that unstable patterns of behavior and a reduction in motor activity were observed in IC compared with those in EC. Furthermore, no significant changes in peripheral leukocytes were observed, while plasma epinephrine and cortisol transiently increased after the series of stimulations, but immediately decreased after the end of the stimulation in EC. On the other hand, there was a greater and prolonged increase in the number of peripheral granulocytes and the plasma levels of epinephrine and cortisol from 1 to 2 h after the stimulation until the end of the experiment in IC. Regarding the number of peripheral lymphocytes, CD4+ or CD8+ lymphocytes and the CD4+ to CD8+ ratio, no significant differences were found between EC and IC. These results suggest that the inability to escape from the aversive stimulation caused a decrease in movement and a prolonged alteration of the immune and endocrine systems, as is often observed in learned helplessness.