Transforming growth factor beta-1 is involved in local signaling for a variety of human diseases including renal diseases, cardiac hypertrophy and fibrosis in heart failure, hepatic fibrosis, and pulmonary fibrosis. Elevated levels of circulating transforming growth factor beta-1 result in organ fibrosis in animal models. In humans smoking, hypertension, diabetes and obesity appear to result in elevated circulating levels. This paper outlines a hypothesis that elevated circulating levels of transforming growth factor beta-1 are part of the molecular link between several entities that have epidemiologic ties including hypertension, diabetes, smoking and obesity on one hand and diseases resulting in organ fibrosis on the other including renal disease and cardiac fibrosis and hypertrophy in heart failure. Additionally, it is suggested that elevated levels are not simply a marker of a similar mechanism of disease production but that elevated levels of circulating transforming growth factor beta-1 lead to disease production and to the synergy of risk factors seen in production of human fibrotic diseases.