The possibility that Cd administration could activate the pituitary-adrenal axis has been studied. It was found that acute administration of Cd strongly increased serum corticosterone levels. Adrenocortical activation correlated well with serum Cd levels, suggesting that adrenal activation was dependent on the presence of the metal in the blood. In addition, our data clearly demonstrate that increased corticosterone secretion caused by Cd was, at least in part, mediated by adrenocorticotropin release. Therefore, it appears that Cd might cause similar endocrine and metabolic changes as classical stress agents.