Zinc plays an important role in the maintenance of the immune system. While the mechanisms of zinc ions interaction with immune cells are still poorly understood, a striking concurrent effect of zinc is the induction of the biosynthesis of metallothioneins (MT), a group of low molecular weight, cysteine-rich metal-binding proteins, believed to play a role in zinc homeostasis. In humans, they are encoded by a family of genes, located at 16q13 containing 10 functional and 7 non-functional MT isoforms. In this work we analyzed the spectrum of different isoforms in human peripheral blood lymphocytes. It was demonstrated by RT-PCR that the MT-2a, MT-1a, MT-1e, MT-1f, MT-1g, MT-1h and MT-1x genes are expressed in these cells and that these isoforms are further upregulated by zinc, as examined by quantitative RT-PCR. Surprisingly, RT-PCR also showed the presence, even in unstimulated cells, of MT-3 transcripts, which are considered as brain-specific isoforms. In an effort to determine whether MTmRNA abundance is translated into MT protein, MT isolated from zinc-treated lymphocytes by gel chromatography was resolved into 7 metal-binding fractions by using RP-HPLC. Automatic Edman-degradation of the different fractions revealed the presence of MT-2a, MT-1a, MT-1e, MT-1f, MT-1g, MT-1h, MT-1x and MT-1k, an isoform which until now was only identified at the level of protein in human liver and kidney tissue.