Neurons are postmitotic for the adult life of animals. Tumors rarely, if ever, arise from neurons in the adult, although they do from other cells from the same lineage, such as the neuroendocrine C cells of the thyroid. We have found that 2 kb of the calcitonin gene-related peptide (CGRP)/calcitonin gene suffices to target expression to CGRP-containing neurons, such as those in the dorsal root ganglia (DRG), and to the calcitonin-secreting C cells of the thyroid. Using this promoter we have examined the effect of two potentially transforming oncogenes in these two different populations. Overexpression of c-myc for periods of up to two years does not transform either cell type, whereas SV40 Tag causes early onset medullary thyroid carcinoma, but does not transform the dorsal root ganglia neurons. This suggests that as part of the terminal differentiation process of these neurons, the cessation of mitosis is accompanied by a relative refractoriness to oncogenes that may transform other cells of the same lineage.