We have shown that a Mr 37,000 protein whose expression is strongly enhanced in human lung cancer tissues is the subunit of glyceraldehyde-3-phosphate (GAPDH, EC 1.2.1.12). We have isolated a GAPDH complementary DNA from human lung cancer cells and deduced the complete amino acid sequence of the encoded protein. The structure of the lung cancer GAPDH is identical to that of liver GAPDH. In addition, we have found that GAPDH mRNA expression is markedly increased in human lung cancer tissues. These results disclose a molecular basis of increased glycolysis in cancer cells and reveal an important role of energy creating reaction in cancer cell growth.