21-hydroxylase converts progesterone to 11-deoxycorticosterone and 17-hydroxyprogesterone to 11-deoxycortisol, the substrates which are required for the production of the main adrenal steroids, corticosterone, aldosterone, and cortisol. As 21-hydroxylase activity has been detected in rodent and fetal human brain, we studied whether and to what extent 21-hydroxylase mRNA is expressed in hippocampal tissue specimens from patients undergoing epilepsy surgery (n=42). 21-hydroxylase mRNA was detected in the hippocampus with an expression 10 000 times lower than in adrenal gland tissue. There was no significant difference in expression levels between women (9.5+/-2.7 arbitrary units (aU); mean+/-SEM) and men (8.0+/-2.2 aU); however, mRNA concentrations in the hippocampus of children (n=4, 1.8+/-0.5 aU) were considerably lower than in adults (n=38, 8.6+/-1.7 aU). The expression of 21-hydroxylase mRNA in the hippocampus suggests that this human brain area has the enzymatic capability to convert progesterone to 11-deoxycorticosterone and 17-hydroxyprogesterone to 11-deoxycortisol.