The agouti protein is known to compete with the melanocortin hormones (ACTH, melanocyte-stimulating hormone) at melanocortin receptors, which in turn are involved in controlling the central and peripheral components of the hypothalamo-hypophyseal-adrenal system. The aim of the present work was therefore to assess the effects of the dominant mutation Agouti yellow (A(y)/a), which induces ectopic hyperproduction of the agouti protein and yellow coat color, on the function of the hypothalamo-hypophyseal-adrenal system. Experiments were performed on male A(y)/a mice of the C57BI/6J line. Controls consisted of mice of the same line bearing the recessive mutation nonagouti (a/a), which leads to the absence of agouti protein and black coat color. The experimental results showed that mice with different agouti genotypes had identical basal corticosterone levels, though yellow mice, as compared with black mice, had increased corticosterone levels after restriction stress (p < 0.02), along with decreased stress reactivity after treatment with dexamethasone (p < 0.0007), and increased adrenal sensitivity to small doses of activity, both in vitro and in vivo.