Pancreatic cancer continues to be a lethal disease and ranks as the fifth major cause of cancer death with a 2-year survival rate of only 8%. Although significant progress has been made in the surgical management of this malignancy, there have been only minimal advances in adjuvant therapy. Based on the lack of effective adjuvant or primary therapy for these patients, we tested the effects of various retinoids (all-trans, 9-cis, and 13-cis retinoic acids) on the growth of several human pancreatic cancer cell lines. Four human pancreatic cancer cell lines, designated PANC-1, ASPC, BxPc, and HPAF, were studied. Three types of retinoic acid were added to subconfluent monolayers of the different cancer cell lines over a range of concentrations (1 to 20 μmol/L). Effects on cell growth were determined daily over 96 hours by a cell proliferation assay (MTT). Nuclear receptor (RAR/RXR) transcript and protein were determined by reverse transcription polymerase chain reaction and Western blot analyses. Three (PANC-1, ASPC, and BxPc) pancreatic cancer cell lines responded in a dose-dependent fashion with a significant decrease in cell growth at clinically relevant concentrations of 9-cis retinoic acid (7.5 to 10 μmol/L). All-trans and 13-cis retinoic acid did not affect cell growth in the four pancreatic tumors.