Various stress conditions including exposure to low-dose radiation and low concentrations of chemical mutagens can induce an adaptive response to subsequent radiation-induced chromosome damage. In this study, the effect of pretreatment of rabbit lymphocytes with zinc or copper salts on radiation-induced chromosome damage was investigated. Pretreatment of rabbit peripheral lymphocytes with Zn (50 microM in vitro or 100 mumol/g body weight in vivo) resulted in resistance to gamma radiation (2.0 Gy)-induced chromosome aberrations such as dicentrics plus centric rings and cells with chromosome aberrations. On the other hand, pretreatment with Cu (50 microM in vitro) did not show any protective effect on radiation-induced chromosome damage in rabbit lymphocytes. However, the concentration of metallothionein increased in activated lymphocytes 24 h after in vitro pretreatment with both Zn and Cu. In addition, gamma-radiation-induced calf thymus DNA damage could be prevented directly by the addition of Zn-metallothionein in the cell-free system. These results suggest that the induction of zinc-metallothionein synthesis may act as one of the defensive mechanisms to the induction of cytogenetic adaptive response to ionizing radiation while copper-metallothionein did not show any radioprotective effect.