The rodent testes are generally more susceptible to cadmium(Cd)-induced toxicity than the liver. In order to clarify the molecular mechanism underlying tissue and cell differences in Cd sensitivity, metallothionein(MT) gene expression, MT protein accumulation, and Cd retention were compared under different time in freshly isolated testicular sertoli cells and liver of rats treated with Cd. Adult male Sprague-Dawley rats received a s.c. injection of 4.0 μmol/kg and 0 h(control), 1 h, 3 h, 6 h, or 24 h later, tissue were sampled and testicular sertoli cells were isolated. MT1 and MT2 mRNA levels were determined by semi-quantitative RT-PCR analysis followed by densitometry scanning, and MT was estimated by the enzyme-linked immunosorbent assay (ELISA) method. Cadmium content was determined by atomic absorption spectrophotometry. The results demonstrated that both isoform mRNA: MT1 and MT2 were increased after Cd treatment in liver and peaked at 3h, followed by a decline, in contrast, the mRNA levels in sertoli cells peaked at 6h. Cd exposure substantially increased hepatic MT, but did not increase MT translation in sertoli cells. These results indicate that: (1)metallothionein mRNA expression is tissue- and time-dependent; (2) the inability to induce the metal-detoxicating MT-protein in response to Cd, might account for higher susceptibility of testes to Cd toxicity and carcinogenesis relative to liver.