In a human medullary thyroid carcinoma (TT) cell line, expression of the calcitonin (CT)/CT gene-related peptide (CGRP-I) gene (CALC-I or alpha) at the level of mRNA and of encoded peptides is higher than that of the closely related CGRP-II gene (CALC-II or beta). In response to 1 mM dibutyryl cAMP ((Bu)2cAMP), mature CGRP-II mRNA and intact cellular CGRP-II were raised 65- and 10-fold, respectively, at 72 h. Also at 72 h, 1 mM sodium butyrate enhanced CGRP-II mRNA only 9-fold and cellular CGRP-II 2-fold; stimulation of CGRP-I and CT mRNA and of cellular CGRP-I and CT by both (Bu)2cAMP and sodium butyrate was similarly low. During the same incubation time period secreted CGRP-II was raised 44-fold in response to (Bu)2cAMP, and CGRP-I and CT 8- and 42-fold, respectively. In conclusion, gene products of CALC-I (CGRP-I and CT) are present in higher amounts in TT cells than those of CALC-II (CGRP II). Yet (Bu)2cAMP predominantly stimulates the expression of CALC-II.