Human peripheral blood lymphocytes (PBLs) produce metallothioneins (MTs) in response to a variety of heavy metal ions. MTs could therefore be a candidate for a marker that represents the biological effect of heavy metals. Since it is practically difficult to measure MT protein levels in PBLs, we examined if MT-mRNA could serve as a biomarker of heavy metal exposure. It is difficult to obtain RNA from PBLs without degradation, but we found that intact RNA can be prepared by the acid guanidinium thiocyanate-phenol-chloroform extraction method which minimizes nuclease digestion of RNA during purification steps. By Northern blot analysis of RNA isolated by this method from PBLs cultured with or without CdSO4, we demonstrated that MT-mRNA is induced by 0.1 to 0.5 microM CdSO4 in a dose-dependent manner. The blood cadmium levels of exposed humans have been reported to be up to 0.5 microM. This suggests that our assay is able to detect quantitative changes in the PBL MT-mRNA level resulting from in vivo cadmium exposure. Thus, PBL MT-mRNA could be used as a sensitive biomarker reflecting exposure to cadmium, and probably to several other MT-inducing heavy metals.