In this study, induction of the isoforms of metallothionein (MT) by Cd and Zn was determined with a high-performance liquid chromatography method. Rats were injected (sc) with Cd (1-100 mumol/kg) or Zn (100-10,000 mumol/kg) and concentrations of MT-I and MT-II in liver, kidney, and pancreas were measured 24 hr later. In control rats, only MT-II was detected in liver, whereas both forms were detected in kidney. In liver, Cd treatment increased MTs at all dosages tested such that concentrations of MT-I and MT-II were approximately equal. Zn (100-1000 mumol/kg) increased concentrations of MT-II about three times higher than MT-I, but higher dosages increased both isoforms to similar levels. Time-course experiments indicated that, at all times after Cd administration (30 mumol/kg), concentrations of MT-I and MT-II in liver were similar. However, with Zn treatment (1000 mumol/kg), MT-II levels were three times higher than MT-I at all times after 6 hr. In kidney, no differences in induction of the isoforms was observed following Cd or Zn treatment. In pancreas, Zn (300-10,000 mumol/kg) induced MT-I and MT-II to similar levels. Thus, in liver and kidney, Cd induced MT-I and MT-II similarly over a wide range of dosages. However, Zn treatment preferentially increased hepatic MT-II at low dosages but induced MT-I and MT-II to similar levels at high dosages. In contrast, Zn induced MT-I and MT-II to similar levels in kidney and pancreas.