Sleep impairment is one of the major side effects of glucocorticoid therapy. The mechanism responsible for this circadian disorder is unknown, but alterations in the suprachiasmatic nucleus (SCN), the biological clock of the human brain, are presumed to play a major role. In the present study, the amount of vasopressin mRNA (AVP mRNA) expression in the SCN was investigated in 10 glucocorticoid-exposed patients and 10 glucocorticoid free, age- and clock time of death-matched controls. The total amount of AVP mRNA, expressed as masked silver grains in the SCN, was two times lower in glucocorticoid-exposed patients (n = 10; 5115 +/- 1314 microm(2)) than that in controls (n = 10; 11,021 +/- 1408 microm(2)) (P = 0.006). There was also a 53% decrease in the total number of profiles in the SCN that expressed AVP mRNA in glucocorticoid-exposed patients (16,759 +/- 3110) compared with those in controls (31,490 +/- 3816) (P = 0.01). In conclusion, glucocorticoids have an inhibitory effect on AVP mRNA expression in the human SCN, which may be the biological basis of the circadian rhythm disturbances during glucocorticoid therapy.