Chondrocytes in the fetal skull and visceral cartilage are considered to be of neural crest origin1 while those found elsewhere in the body are thought to be derived from mesoderm2,3 (mesodermal chondrocytes). Chondrocytes of pelvic rudiments from chick embryos are the only cells known to respond to nerve growth factor that are not of neuroectodermal origin4. In addition, embryonic spinal cord5 and neural retina6 of chickens synthesize type II collagen5,6, originally thought to be confined to cartilage. Here we report the presence of the S-100 protein (S-100) in chondrocytes of skull, vertebrae, ribs, sternum, larynx and long bones of the human fetus, and larynx and xiphoid process of the human adult. Mesodermal chondrocytes are the only cells which contain S-100 and yet are not considered to be of neuroectodermal origin, thus our results indicate that these chondrocytes may be developmentally closer to neuroectoderm than traditionally thought.