The expression of the natural killer cell-associated antigens CD56 and CD57 which are known to show sequence homologies to the neural cell adhesion molecule N-CAM was examined immunohistochemically in normal and regenerative human neural and straited muscle cells and in their tumors using monoclonal antibodies Leu-19 and Leu-7. The pattern of expression of CD56 and CD57 in neural tissue was assessed in comparison with that of Mr 68,000 neurofilament. Dendritic interstitial cells were discriminated from neural cells by application of the pan leukocyte antigen CD53. In normal tissue, CD56 was expressed in thin nerve fibers, fine varicose and sensory nerve endings, cell membranes of ganglion cells, and fetal striated muscle cells. Thick nerve fibers, perikarya of ganglion cells, and adult striated muscle fibers were CD56 negative. In the normal state, CD57 was restricted to thick nerve fibers. Enhanced expression or reexpression of CD56 was found in regenerative neural cells which, in part, were also CD57 positive and in regenerative, CD57-negative striated muscle cells. In neural tumors, CD56 was detectable in 3 of 3 benign and 8 of 13 malignant schwannomas, 1 of 4 peripheral neuroepitheliomas, 4 of 4 ganglioneuromas, and 8 of 8 (ganglio-)neuroblastomas, whereas CD57 was restricted to one benign and one malignant schwannoma. Furthermore, CD56, but not CD57, could be found in 8 of 8 rhabdomyosarcomas. All in all, the pattern of expression of CD56 is comparable to that of N-CAM. CD57 exhibits a very restricted binding pattern which, in most instances, is complementary to that of CD56. The absence of CD56 in some neural tumors might reflect alterations in cell-cell interactions. Its reexpression in regenerative striated muscle cells and in rhabdomyosarcomas suggests a role of CD56 as an oncodevelopmental antigen.