Northern blot analysis was used to investigate the effect of dexamethasone (Dex) or zinc on messenger RNA (mRNA) levels of metallothionein-IIa (MT-IIa) in fibroblasts from a patient with cortisol hyperreactive syndrome and from three normal subjects. Dex was seen to increase MT-IIa mRNA levels and brought them to a maximum after 12 h. Zinc also increased the levels of MT-IIa mRNA and brought them to a maximum at 8 h after the addition. Dex as well as zinc caused a dose-related increase in MT-IIa mRNA levels. Dex had a maximal inductive effect on MT-IIa at a concentration of 10(-6) mol/L and zinc at a concentration of 10(-4) mol/L. There was no significant difference in the levels of basal expression of the MT-IIa gene between the patient's and normal fibroblasts. But in three separate experiments induction of MT-IIa gene by Dex obtained for the patient's fibroblasts was almost twice as much as that for normal fibroblasts. On the other hand, there were no significant difference in induction by zinc between the patient's and normal fibroblasts. These data indicated that the patient's cells were hyperreactive to glucocorticoids as seen from the effect of Dex on the MT-IIa mRNA levels.