Partial purification of the DNA ligase from three human tissues (liver, thymus and lymphoblasts) revealed that each cell type contains several different polypeptides bearing a DNA ligase I activity. Their apparent molecular weights estimated after SDS PAGE, 130 kDa, 100 kDa and 80 kDa, are in agreement with previous reports. These polypeptides are related by proteolysis to a single higher molecular weight protein of 200 kDa which does not show DNA ligase activity but that could be a preprotein.