Intermediate filaments are a third cytoskeletal system in animal cells, distinct from microfilaments and microtubules. They range in diameter from 6–11 nm and include tonofilaments, neurofilaments, and various cultured cell filaments. This study differentiates between two types of intermediate filaments: vimentin and prekeratin. Vimentin is a major protein in intermediate filaments of mesenchymal cells, including transformed cells, and is not found in epithelial cells. Prekeratin is found in epithelial cells and epithelia-derived tumor cells, but not in mesenchymal cells. Vimentin is identified as a 57,000 molecular weight protein in mouse 3T3 cells. Antibodies against vimentin decorate intermediate filament arrays in mesenchymal cells but not in epithelial cells. In contrast, antibodies against prekeratin decorate intermediate filament arrays in epithelial cells but not in mesenchymal cells. These findings show that intermediate filaments with similar ultrastructure and solubility characteristics can be distinguished immunologically. Vimentin is proposed as the name for this protein. The study also shows that vimentin is present in various mesenchymal cells and is not found in muscle or brain tissues. The results indicate that intermediate filaments are distinct in different cell types and that vimentin and prekeratin represent two different systems of intermediate filaments.Intermediate filaments are a third cytoskeletal system in animal cells, distinct from microfilaments and microtubules. They range in diameter from 6–11 nm and include tonofilaments, neurofilaments, and various cultured cell filaments. This study differentiates between two types of intermediate filaments: vimentin and prekeratin. Vimentin is a major protein in intermediate filaments of mesenchymal cells, including transformed cells, and is not found in epithelial cells. Prekeratin is found in epithelial cells and epithelia-derived tumor cells, but not in mesenchymal cells. Vimentin is identified as a 57,000 molecular weight protein in mouse 3T3 cells. Antibodies against vimentin decorate intermediate filament arrays in mesenchymal cells but not in epithelial cells. In contrast, antibodies against prekeratin decorate intermediate filament arrays in epithelial cells but not in mesenchymal cells. These findings show that intermediate filaments with similar ultrastructure and solubility characteristics can be distinguished immunologically. Vimentin is proposed as the name for this protein. The study also shows that vimentin is present in various mesenchymal cells and is not found in muscle or brain tissues. The results indicate that intermediate filaments are distinct in different cell types and that vimentin and prekeratin represent two different systems of intermediate filaments.