SCG10 is a neural-specific, growth-associated protein that is broadly expressed in the embryonic central and peripheral nervous systems. Transgenic mice harboring a chimeric gene containing 4 kb of SCG10 5' flanking DNA fused to the bacterial CAT gene exhibit expression in brain but not in nonneuronal tissues. A low level of expression is detected in adrenal gland as well, consistent with the behavior of endogenous SCG10. Such a transgene is also activated at the same relative stage of embryonic development as its endogenous counterpart. Deletion of the 5'-most 3.7 kb of SCG10 sequence yields deregulated expression of the transgene in numerous nonneuronal tissues, although expression remains highest in brain. In contrast to other tissue-specific genes, therefore, the specificity of SCG10 expression appears to be achieved predominantly through selective repression in nonneuronal tissues.