Carbonic anhydrase II (CA II) generates bicarbonate in human pancreatic duct cells. We have developed the human pancreatic duct cell line DANG as a model to study the effects of all-trans-retinoic acid (ATRA) on CA II gene expression. ATRA treatment resulted in a time- and dose-dependent inhibition of CA II mRNA concentrations in DANG cells. These inhibitory effects were paralleled by a time-dependent decrease of CA II protein concentrations. Nuclear run on analysis revealed that the decrease of CA II mRNA concentrations was due to a decreased rate of CA II gene transcription. These data show that ATRA transcriptionally modulates CA II gene expression in human pancreatic carcinoma cells.