Myocardial hypertrophy is associated with an increase in myocyte volume that requires enhanced protein synthesis. If the amount of newly synthesized protein exceeds the ER protein folding capability, the ER triggers a stress reaction that serves to reduce the protein biosynthesis load and to enhance the folding capacity. At present it is unclear which roles biomechanical load and neurohumoral activation, respectively, play during the development of hypertrophy-associated ER stress. We assessed mRNA expression levels of ER molecular chaperones (realtime PCR) in RV and LV myocardium of monocrotaline-treated (MCT) rats that had developed chronic pressure-induced RV hypertrophy as well as in rabbit right ventricular papillary muscles acutely subjected to biomechanical load over 6h in a long-term muscle strip culture system. RV myocardium of MCT rats (n=6) expressed enhanced levels of the ER molecular chaperones "binding protein" and calreticulin (BiP/GaPDH; 0,067±0,01 vs. 0,04±0,004, P=0,05) and (CRT/GaPDH; 0,19±0,03 vs. 0,08±0,004, P=0,008), compared to control (n=6) RV myocardium. In contrast, no significant alterations were observed in LV myocardium of MCT rats. 6h of stretch (n=6) upregulated BiP (by 68 %, P=0.03), compared to unloaded muscle strips (n=4), while CRT expression was not significantly altered. Our data demonstrate that enhanced biomechanical load is sufficient and neurohumoral stimulation not necessary to induce ER stress in the myocardium.