The induction of metallothionein (MT) synthesis in the brain was investigated in MT-I isoform-overexpressing transgenic (MT-I*) and control mice after exposure to increasing doses of 2 to 20 Gy of whole-body gamma radiation. Although the MT-I isoform was the major isoform of MT in this transgenic mouse, the other isoforms, MT-II and MT-III, were also present in the brain. The total concentration of MT in the brain was measured by a cadmium-binding assay, while zinc and lipid peroxides were measured by atomic absorption spectrophotometry and by the thiobarbituric acid method, respectively. In MT-I* mice at 24 h after radiation exposure, the level of MT in the brain was increased from a basal level of 44.4 +/- 4.0 microg/g to a maximum level of 91.0 +/- 9.0 microg/g after 5 Gy and remained high after 10 and 20 Gy. In a time-course experiment with 5 Gy, the concentration of MT in the brain of MT-I* mice increased at 3 h and reached a maximum of 175.3 +/- 15.3 microg/g at 6 h. This high level of MT remained unchanged for 48 h after radiation exposure. Metallothionein was not induced markedly in the brains of control mice either at 24 h after exposure to 2-20 Gy gamma radiation or at different times after exposure to 5 Gy gamma radiation. In both strains of mice, the total concentration of zinc in the brain decreased with increasing radiation dose. No differences in lipid peroxide levels were seen in control mice exposed to 5 Gy at 6 and 12 h or after exposure to three other doses (2, 10 and 20 Gy) at 24 h. Slight increases (1.35 and 1.22, respectively) in lipid peroxide levels were observed in control mice at 24 and 48 h after exposure to 5 Gy. Lipid peroxide levels in the brain were not changed in irradiated MT-I* mice. The results show a marked increase in the levels of MT in the brain of transgenic mice after exposure to gamma radiation. The induced synthesis of MT may be only one of several mechanisms that prevent the induction of lipid peroxidation in the brain by gamma radiation.