The differentiation of human embryo chondrocytes was markedly induced by the addition of Bt2cAMP to the culture medium. Using this culture system, a novel human cDNA for a basic helix-loop-helix (bHLH) protein (named DEC1) expressed primarily in the chondrocytes in response to Bt2cAMP was cloned by the subtractive hybridization method. DEC1 protein consists of 412 amino acids and exhibits structural similarities to the mammalian HES family, Drosophila hairy, and Enhancer of split m7 in the bHLH region. Northern blot analysis showed that DEC1 mRNA was expressed in various tissues including the cartilage, lung, spleen, and intestine, but not in the brain. These findings suggest that the bHLH factor DEC is involved in the control of cell differentiation in several tissues including cartilage.