BACKGROUND Four cardiac hormones, i.e. atrial natriuretic peptide (ANP), vessel dilator, long-acting natriuretic peptide (LANP) and kaliuretic peptide (KP), have anticancer effects both in vitro and in vivo. The sustained decrease in number of human pancreatic adenocarcinoma cells for 3 days secondary to the four hormones noted previously suggests a decrease in proliferation of pancreatic cancer cells not eliminated after initial treatment. METHODS Four cardiac hormones were evaluated for their ability to directly decrease proliferation of human pancreatic cancer cells with comparison of their effects on proliferation on normal human lung, kidney, prostate and endothelial cells. RESULTS ANP, LANP, vessel dilator and KP decreased the proliferation of viable human pancreatic adenocarcinoma cells by 39%, 73%, 26% and 32% respectively at their 0.01 microM concentrations compared with the proliferation of untreated pancreatic cancer cells. Maximal inhibition of proliferation (81%) occurred with LANP at its 0.1 microM concentration in dose-response studies. At these same concentrations, there was no decrease in proliferation of human kidney, lung, prostate or endothelial cells compared with untreated kidney, lung, prostate or endothelial cells. CONCLUSIONS Four cardiac hormones have strong anti-proliferative effects on human pancreatic adenocarcinoma cells while sparing human kidney, lung, prostate and endothelial cells from a similar strong anti-proliferative effect. This anti-proliferative effect on pancreatic cancer cells helps to explain why human pancreatic cancers in vivo treated with the cardiac hormones decrease to less than 10% of the volume of untreated pancreatic cancers as they proliferate less.