Mast cells (MCs) are amine-storing cells with heterogeneous histological, biochemical, and functional properties. They are found in connective tissue as well as in the peripheral and central nervous system (CNS) of many mammalian species. In this study we investigated whether the distribution of MCs in the CNS of adult male CD-1 mice was modified following repeated defeat stress. Experimental subjects underwent a 3-week period of fighting encounters with a highly aggressive resident. On the test day they were divided into three groups: (a) paired with the resident for 20 min; (b) placed in a cage containing the soiled bedding of the resident for 20 min; (c) placed in a cage with clean sawdust for 20 min. Results show that previous defeat stress increases the number of MCs in the thalamus, habenula, and hypothalamus of subjects exposed to a fighting opponent or to a clean cage, compared to subjects placed in a cage with the bedding of the opponent or to a group-housed, nondefeated control. These results, together with previous reports in birds and rodents, suggest that MCs have a wider role than previously expected and might be involved in the behavioral response to highly relevant psychosocial stimuli.