Myocardial stiffening, chamber dilatation and contractile dysfunction occur during the progression to cardiac failure and during this process considerable remodelling of the myocardial extracellular matrix is thought to occur. Although previous studies of hypertensive heart disease have described an accumulation of collagen (interstitial fibrosis) at failure (1), others have observed increased matrix degradation by an increased activity of matrix metalloproteases (MMPs) (2). It remains to be fully determined how extracellular matrix turnover is altered when cardiac dilatation precedes heart failure. We have previously reported a ferret model of heart failure which exhibits hypertrophy followed by chamber dilatation and contractile dysfunction (3,4). When heart failure was induced by aortic coarctation, animals were anaesthetised with an intramuscular injection 70mg kg ^-1 medetomidine- 7mg kg ^-1 ketamine. Carpofen analgesic (5 mg kg ^-1 ) was administered pre-operatively. Animals were humanely killed with pentobarbitone sodium (200 mg kg ^-1) administered intraperitoneally at the onset of the symptons of heart failure. Using this animal model we found that, in the hypertrophic myocardium prior to symptoms of heart failure, the mean collagen content per dry weight of tissue was reduced compared to sham operated animals (2.6 ± 0.3% vs 3.5 ± 0.4%, n = 6, p < 0.05 unpaired t-test) and further reduced at failure (2.2 ± 0.3% vs 3.5 ± 0.4%, n = 6, p < 0.05 unpaired t-test). In agreement, histological staining of myocardial collagen in paraffin embedded sections also revealed the collagen content, as measured per tissue section area, was reduced at failure compared with sham (1.0 ± 0.2% vs 2.8 ± 0.3% p < 0.001 unpaired t-test). We also went on to investigate the changes in matrix metalloprotease activity at the same time points using gelatin zymography on myocardial extracts followed by densitometric analysis of lytic bands. An increased activity in two elastin-degrading matrix metalloproteinases MMP-2 and 9 was observed. Mean MMP-9 band density was not significantly altered in hypertrophic myocardium (taken from individuals lacking symptoms of CHF) compared to sham controls (n=10), but increased by 200% at HF (n=10, p < 0.001 unpaired t-test). The mean ratio between pro and active forms of MMP-2 decreased by 22% in hypertrophic myocardium (n=10, p = 0.013 unpaired t-test) and decreased by 47% at HF (n=10, p < 0.001 unpaired t-test) compared with sham control. This differentially increased activity in MMP-2 and 9 at failure could partly explain progressive decrease in the collagenous matrix of the myocardium contributing to left ventricular chamber dilatation at heart failure.