BACKGROUND AND PURPOSE: The β1 -adrenoceptor has at least two binding sites, high and low affinity sites (β1H and β1L , respectively), which mediate cardiostimulation. While β1H - adrenoceptor can be blocked by all clinically used β-blockers, β1L -adrenoceptor is relatively resistant to blockade. Thus, chronic β1L -adrenoceptor activation may mediate persistent cardiostimulation, despite the concurrent blockade of β1H -adrenoceptors. It is important to determine the potential significance of β1L -adrenoceptors in vivo, particularly in the setting of disease. EXPERIMENTAL APPROACH: C57Bl/6 male mice were used. Chronic (4 or 8 weeks) β1L -adrenoceptor activation was achieved by treatment, via osmotic minipumps, with (-)-CGP12177 (10 mg kg-1 day-1 ). Cardiac function was assessed by echocardiography and micromanometry. KEY RESULTS: (-)-CGP12177 treatment in healthy mice increased heart rate and left ventricular (LV) contractility. In mice subjected to transverse aorta constriction (TAC), (-)-CGP12177 treatment during 4-8 or 4-12 weeks, respectively, after TAC led to a positive inotropic effect and exacerbated fibrogenic signalling while cardiac hypertrophy tended to be more severe. (-)-CGP12177 treatment to mice with TAC exacerbated myocardial expression of hypertrophic, fibrogenic and inflammatory genes (all P<0.05 vs. non-treated mice with aorta banding). Washout of (-)-CGP12177 revealed a more pronounced cardiac dysfunction after 12 weeks TAC. CONCLUSIONS AND IMPLICATIONS: β1L -adrenoceptor activation provides functional support to the heart, in both normal and diseased (pressure overload) settings. Sustained β1L -adrenoceptor activation in the diseased heart exacerbates LV remodelling and therefore may promote disease progression from compensatory hypertrophy to heart failure. This article is protected by copyright. All rights reserved.