We studied the urinary excretion of transforming growth factor-beta 1 (TGF-beta 1), platelet-derived growth factor-BB (PDGF) and fibronectin (FN) in 104 patients (52 normoalbuminuric, 24 microalbuminuric, and 28 with overt diabetic nephropathy) with insulin-dependent diabetes mellitus (IDDM) of a long duration and in 30 non-diabetic controls. IDDM patients had higher urinary excretion of TGF-beta 1, PDGF and FN compared to controls. Urinary excretion of TGF-beta 1 and PDGF was elevated in all IDDM subgroups, while FN excretion was significantly increased only in patients with macroalbuminuria. Urinary excretion of TGF-beta 1 and FN did not differ between normoalbuminuric IDDM patients with long duration of diabetes, a group at low risk of ever developing diabetic nephropathy, and IDDM patients with incipient or overt diabetic nephropathy. Excretion of PDGF was significantly higher in patients with micro- and macroalbuminuria compared to normoalbuminuric patients, but there was a considerable overlap between the groups. In conclusion, although longitudinal follow-up studies are needed to further clarify the issue, our results in long-standing IDDM do not support a hypothesis of urinary excretion of TGF-beta 1, PDGF or FN to predict development of diabetic nephropathy.