Alternative RNA processing of the calcltonln/CGRP gene generates transcripts encoding predominantly calcitonin in thyroid C cells or CGRP In the nervous mystem. To examine the RNA processing choice of this gene In a wide variety of tissues, we created transgenlc mice expressing the rat calcitonin/CGRP transcript from the mouse metallothlonein-I promoter. Most cells that do not express the endogenous calcltonin/CGRP gene have the capability to make a clear splicing choice for calcltonin or CGRP transcript. In the majority of tissues studied, 90% 47% of the transgene mRNA encodes calcitonin. In contrast, both calcltonln and CGRP mRNAs wem detected in the tranagenie mice brains. lmmunohistochemical and In situ RNA hybridization analyses show that CGRP transcripts an selectively expressed In a wide variety of neurons, while calcltonin Is expressed predominantly In nonneuronal structurea Splicing choice operates independently of calcltonln/CGRP gene transcription. The data suggest that a specific regulatory machinery is required for the proassing of CGRP transcripts and is restricted prlmarlly to neurons.