The selective control of gene expression results in diversified morphology and physiological function. Understanding the expression of differentiated function in molecular terms requires detailed characterization of the regulation of mRNA synthesis and catabolism. Although considerable emphasis has been placed on transcriptional control, the discovery of HnRNA and `split genes' gives rise to the possibility of post-transcriptional regulation at the level of processing of nuclear precursors1,2. A rat calcitonin-producing medullary thyroid carcinoma (MTC) line was used as a model for definition of certain aspects in regulation of gene expression. Serial transplantation of several rat MTC lines containing and secreting large amounts of calcitonin generated tumours in which calcitonin biosynthesis was decreased more than 10-fold. We report here that the conversion from a `high' to a `low' calcitonin producing state is associated with specific modifications of the calcitonin mRNA synthetic pathway and a consequence of these changes seems to be the production of a new cytoplasmic mRNA.