To examine the role of metallothionein on Ag accumulation in liver or kidney of rat after Ag injection, the relative Ag-binding capacity of Ag-induced metallothionein in hepatic or renal cytosol of rat after Ag injection was determined. The greater part of Ag increment in hepatic cytosol was attributable to a low molecular weight protein, while the main part of Ag increment in renal cytosol was ascribed to high molecular weight proteins. The low molecular weight, metal-binding protein was identified as metallothionein using ELISA. The maximal levels of hepatic and renal metallothionein mRNA induced by Ag occurred at 7 hr after Ag injection. There was a close relationship between Ag contents in the hepatic or renal cytosol and metallothionein after Ag injection. In dose-response and time-course studies, approximately 60-70% of the Ag increments in hepatic cytosol and approximately 30% of the Ag increments in renal cytosol were bound to metallothionein. These results suggest that the role of metallothionein on Ag accumulation in the liver after Ag injection is different from that of metallothionein on Ag accumulation in the kidney.