Synapsins are neuron-specific phosphoproteins of small synaptic vesicles encoded by two different genes. While the gene for synapsin I (SYN1) is on the X chromosome, we have now assigned the human and mouse synapsin II (SYN2) genes to autosomes. By using PCR primers derived from rat synapsin II cDNA sequences we were able to amplify homologous sequences of the 3'-untranslated regions and to localize the human SYN2 gene to 3p and the mouse Syn2 gene to mouse chromosome 6 by single strand conformation analysis of PCR products from panels of somatic hybrid cell lines. The mouse gene was further mapped by FISH to chromosome 6 band F in a region of known conserved synteny with human 3p. Genotyping of a M. musculus x M. spretus backcross panel placed Syn2 close to a cluster of previously mapped loci on chromosome 6 in an interval between interleukin 5 receptor alpha (Il5ra) and hematopoietic cell phosphatase 1C (Hcph). Both physical and genetic mapping data indicate that Syn2 is near two mutant loci defined by neuromuscular disorders, opisthotonus (opt) and deaf waddler (dfw).