There are two different classes of humoral growth factors for arterial smooth muscle and endothelial cells that age of potential relevance for the development of macrovascular disease inn diabetes mellitus: hormones (growth hormone, insulin like growth factor I and II, insulin) and locally released growth factors of platelet origin. The following hormones have to be considered: Increased growth hormone plasma levels might contribute to macrovascular disease, but its actual relevance remains to be determined. Insulin like growth factor I and II are present in vivo and stimulate growth of vascular cells in vitro but their relevance for macrovascular disease in diabetes is unproven. To insulin, see Dr. Stout's paper. Human platelets contain at least six growth peptides or proteins that all stimulate in vitro growth of arterial wall cells: platelet derived growth factor, epidermal growth factor, platelet derived endothelial cell mitogen, endothelial growth factor, diabetic serum growth factor (DSGF), transforming growth factor-beta. As their plasma concentrations have not been shown to be increased in diabetes increased local availability at sites of stimulated platelet aggregation has been postulated. Therefore, their relevance for macrovascular disease i diabetics is based mainly on circumstantial evidence. The concentration of DSGF of platelet origin depends on the metabolic control: it increases in vivo in poorly controlled diabetics and is normalized after 2-3 weeks of good metabolic control in the same diabetic patient. The growth potency of DSGF from poorly controlled diabetics is greater than that of physiological amounts of insulin or growth hormone.(ABSTRACT TRUNCATED AT 250 WORDS)