Both metallothionein I and II were disrupted using the same targeting construct. Exon 1 of metallothionein I was disrupted by insertion of a 20 bp synthetic oligomer just downstream from the start codon which caused a frame shift. Northern blot analysis of liver mRNA from homozygotes in which the gene was induced by intraperitoneal injection of copper indicated that transcription did take place in spite of the frame shift. However, translation of the protein product did not occur.