Cardiac fibroblasts constitute the majority of the non-myocyte cell population in the ventricular myocardium. These cells are located in the interstitium, in areas between and surrounding cardiac myocytes. Cardiac fibroblasts are responsible for the synthesis of extracellular matrix proteins such as fibrillar collagen types I and III, basement membrane type IV collagen, fibronectin, and laminin. In addition to its role in muscle development and myoblast differentiations, extracellular matrix consisting primarily of fibrillar collagen is an intricate and highly organized structure that serves to support cardiac myocytes and to maintain functional integrity of the myocardium. Balanced synthesis and degradation of this matrix is the key to normal development of cardiac muscle and perfect myocardial function. Collagen remodeling and accumulation has been demonstrated in several experimental models of cardiac hypertrophy. To gain insights into molecular and cellular mechanisms that affect cardiac fibroblast behavior, cardiac fibroblasts from rat and rabbit ventricular myocardium were cultured and the impact of neurotransmitters and growth factors such as norepinephrine and transforming growth factor--beta (TGF-beta 1), to which cardiac fibroblasts are exposed in vivo, was studied. Results of these studies, with regards to gene expression, proliferation and differentiation of cardiac fibroblasts in culture, and their biological implications are discussed.