The pancreas makes two pancreatic proteins [pancreatic lipase-related protein-1 (PLRP-1) and PLRP-2] with marked homology to pancreatic lipase (PL). To determine if a pancreatic acinar cell line, AR42J, also expresses PLRP-1 and PLRP-2, we examined the cells for the presence of PL, PLRP-1, and PLRP-2. RNA blot analysis with specific probes and immunoblot analysis with antipeptide antibodies demonstrated the presence of mRNA and protein for all three homologues in AR42J cells. Additionally, we showed that dexamethasone decreased PLRP-1 mRNA levels twofold and increased PLRP-2 mRNA 20-fold but had little effect on PL or colipase mRNA. Extracellular PLRP-2 protein levels increased threefold, and intracellular PLRP-2 protein levels increased about fourfold. The characteristics of the dexamethasone-induced increase in PLRP-2 mRNA, a rapid change requiring new protein synthesis independent of mRNA turnover, suggested that dexamethasone regulated transcription. We conclude that AR42J cells synthesize and secrete PL, PLRP-1, and PLRP-2 and that dexamethasone discoordinately regulates the expression of the three genes.