Single viable muscle fibers isolated from adult rats by collagenase digestion rapidly bind dissociated spinal neurons or PC-12 cells but not a variety of other cells tested. The adhesion process is calcium-independent, temperature-sensitive, and is not blocked by pretreating cells with inhibitors of energy metabolism or actin polymerization. Adhesion is mediated by a carbohydrate-binding protein and can be inhibited by N-acetylneuraminic acid or mucin, a glycoprotein with high sialic acids content. The hapten inhibitors do not dissociate cells if added after aggregation has occurred. Experiments to block adhesion by pretreatment of cells with either neuraminidase or mucin show that the sialic acids-rich moiety is on the nerve cells, while its receptor is on the muscle fibers.