The cardiac extracellular matrix (ECM) maintains the structural and mechanical integrity of the myocardium. We determined the alterations in the composition of the ECM coincident with the transition from compensated left ventricular hypertrophy (LVH) to symptomatic congestive heart failure (CHF) and the mechanisms underlying such changes. Heart failure was induced in ferrets by aortic banding. Myocardial collagen content was assessed by HPLC and histologically. Matrix metalloproteinase (MMP) activity and tissue inhibitor of metalloproteinase (TIMP) expression were evaluated using gelatin zymography and western blotting respectively. Left ventricular (LV) free wall thickness increased by 29% in asymptomatic LVH and was associated with a 20% increase in interstitial fibrosis (P0.05). CHF was coincident with increased plasma angiotensin II levels (CHF, 149±48; LVH 40±19; sham, 5.6±1pg.ml^-1. P0.01 CHF vs. sham and LVH), ventricular dilatation (LV internal diameter 15±0.4 vs. 9±0.1mm, P0.05), increased active MMP-9 (3.0 and 2.2 fold increase over sham and LVH respectively, n=5-10 animals per group, P0.01) and reduced myocardial total collagen content (3.5±0.4, 2.6±0.3 and 2.2±0.3% in sham, LVH & CHF respectively, P0.05). In CHF the distribution of collagen was found to be markedly altered becoming punctate in nature. No difference in MMP-2 activity, TIMP’s 1-4 nor collagen cross-linking were found at any time point. In summary, the present work demonstrates structural reorganisation and loss of collagen from cardiac ECM during the transition to decompensated CHF. The enhanced MMP-9 activity coincident with the transition to CHF provides potential therapeutic opportunities for managing the progression from asymptomatic LVH to symptomatic CHF.