Fibronectin is present in tissues and also in body fluids (plasma). Both forms were studied in normal controls, diabetics and cancer patients; both of these diseases show an age-dependent increasing trend. Age-dependent variations were shown to occur for both forms of fibronectin. Plasma fibronectin increases exponentially with age in a normal population. This increase is strongly attenuated or absent in diabetics and in mammary cancer patients. On the contrary, tissue fibronectin increases in diabetic skin. In mammary cancer fibronectin disappears from the tumor cell membranes but increases in the peritumoral stroma. The above modifications may be attributed to increased protease activity in tumour tissue and also to the possibility of an increased retention of plasma fibronectin in diabetic skin and peritumoral stroma, both tissues exhibiting a modification of intercellular matrix biosynthesis which does involve the increased production of retention sites of fibronectin. An increased local synthesis in both tissues may also occur. The above results are confronted with those reported by other authors and support the contention that plasma and tissue fibronectins undergo age-dependent modifications which may be seriously perturbed in diabetes and cancer.