The sarcoplasmic reticulum (SR) membrane protein Ca2+‐ATPase (SERCA) helps to regulate intracellular Ca2+ levels, and thus, control arterial tone. We hypothesize that estrogen's (E2) protective effect against vascular disease is partly attributed to the ability of the SR to regulate intracellular Ca2+levels. The aim of this study was to investigate the effect of physiological E2 concentrations on SERCA expression. Right coronary arteries were dissected from female pig hearts. The distal portion of the arteries were sectioned into longitudinal strips and incubated for 24 hours in E2 (1 × 10−9M and 1 × 10−12M). Antibodies reactive to SERCA2, PKG, and PKA were used to determine immunoreactivity in homogenized tissue after the 24 hours of treatment. The results indicate that 1 × 10−9M E2 elicits a 51±8% increase in SERCA2 expression, as well as a corresponding increase in PKG and PKA expression. This suggests that E2 upregulates SERCA2 expression and its regulatory kinases, which may be a protective benefit for pre‐menopausal women. Support: NCRR of the NIH, Grant #P20 RR‐16460