The time course of change in tissue Cd, Cu and Zn contents, their distribution in cellular protein fractions as well as the profile of MT gene expression in mouse liver was described over a 7 days period following a single intraperitoneal injection of 2 mg/kg of CdCl(2). The result showed that Cd accumulated rapidly in mouse liver. Between 1 h and 7 days after administration, over 18% of the total Cd administered were found in the liver. Cd administration was also associated with the overexpression of the MT-mRNA. However, the time course of induction was not parallel to the change in tissue Cd content. When separated on a Sephadex G-75 column, majority of Cd was found to bind to the fractions known to contain the metal-binding protein, metallothionein (MT). From day 2 after Cd administration, a small amount of the metal was also found associated with the high molecular weight (HMW) proteins. In addition to Cd, tissue Zn content was affected most during the entire study. There was a significant decrease in tissue Zn content during the initial 8 h but tissue Zn content increased significantly throughout the following 6 days. At 1-7 days, majority of Zn was associated with the HMW protein fraction. Although there was no significant change in total tissue Cu content, distribution of Cu in different protein fractions was detected. While in control animals, Cu was mainly associated with the HMW proteins, some was found in the MT fraction on the second day. On the 7th day, Cu distribution had deteriorated. Together with changes seen in Cd, the results might suggest that injury had occurred in the tissue at this time. The results of the present study showed that Cd caused a change in subcellular distribution of tissue endogenous metals, which might reflect alteration of cellular functional activities.