OBJECTIVE: Toll-like receptors (TLRs) are involved in a variety of cardiovascular disorders, including myocardial dysfunction during sepsis, ischaemia/reperfusion, heart failure, cardiac hypertrophy, and atherosclerosis. Previous research revealed that TLR4 promotes cardiac hypertrophy in vivo. Therefore, we investigated whether TLR2 and -9 also modulate cardiac hypertrophy induced by transverse aortic constriction (TAC). METHODS: TLR9-deficient (TLR9^-/-), TLR2-deficient (TLR2^-/-) and wild-type (WT, C57Bl/6) mice were subjected to TAC or sham operation procedure (SOP) and inspected after 7 or 14 days. Left ventricular heart and lung weight were determined and hemodynamic parameters were recorded. Real-time RT PCR was used in order to evaluate left ventricular gene expression. RESULTS: TLR2 or TLR9 deficiency did neither influence the development of cardiac hypertrophy nor hemodynamic function after 7 days of pressure overload. Interestingly, lung weight was significantly higher in TLR9 deficient SOP as well as TAC groups than in the matched WT mice. In myocardium, TAC led to a significant elevation of B-type natriuretic peptide (BNP) in both TLR deficient genotypes compared to WT mice. Supposing, that BNP increase may develop an anti- hypertrophic influence on the heart, we determined biometric and hemodynamic parameters after 14 days of TAC in TLR9^-/- mice. Also after this prolonged duration of pressure overload, TLR9 deficiency did not diminish cardiac hypertrophy. CONCLUSION: These findings suggest that following pressure overload TLR2 and TLR9 deficiency does not prevent development of cardiac hypertrophy and dysfunction as does TLR4 deficiency or antagonism. Endogenous ligands released during development of cardiac hypertrophy may bind exclusively to TLR4 and not to TLR2 and -9.