We investigated the effect of interleukin-6 (IL-6) expression on sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA), atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) mRNA levels in cultured rat neonatal ventricular myocytes. IL-6 plays a key role in regulating cardiac hypertrophy and the development of heart failure, and SERCA, ANP and BNP are all cardiac hormones with regulatory properties. Compared with baseline measurements, treatment with 50 U/ml IL-6 significantly decreased SERCA gene expression, but significantly increased ANP and BNP gene expression in the cardiac myocytes. These results suggest that the clinical overproduction of IL-6 in response to infection, autoimmune disease and cancer might be responsible for cardiac hypertrophy. Cardiac hypertrophy may result from the imbalance of both natriuretic peptides and SERCA transcription levels, caused by elevated IL-6 expression.