Disproportionate collagen deposition in the heart impairs cardiac function and may contribute significantly to the poor prognosis of cardiac hypertrophy. Although there has been considerable work elucidating humoral factors which promote myocardial fibrosis much less is known about antifibrotic mechanisms. We propose that atrial and brain natriuretic peptide (ANP and BNP) and nitric oxide (NO) antagonise the effects of fibrotic factors in the myocardium. To address this hypothesis we will: (i) establish the natriuretic peptide receptor subtypes expressed by cardiac fibroblasts; (ii) compare changes in the expression of these subtypes and nitric oxide synthase in cardiac tissue from animal models of cardiac hypertrophy with and without myocardial fibrosis; (iii) examine the effect of ANP, BNP and NO donors on cardiac fibroblast proliferation and collagen synthesis 'in vitro'; and (iv) investigate the effect of a combined neutral- endopeptidase/angiotensin-converting enzyme inhibitor on collagen deposition in the heart 'in vivo'. These studies will provide valuable insight into the role of ANP, BNP and NO in regulating cardiac remodelling and their potential therapeutic value in the treatment of cardiac hypertrophy.