Growth factors circulating with the aqueous may play an important role in the pathogenesis of exfoliation syndrome (XFS), which is characterised by excessive synthesis and accumulation of abnormal extracellular material. We investigated the concentration of three ubiquitous growth factors (TGF-b1, TGF-b2 and IGF-1) in the aqueous humour of 53 patients with XFS and 57 age matched controls. The study was performed by two centres, independent of each other, using different assay systems. Both the total amount of TGF-b1 (90,5 pg/ml in XFS vs 30,2 pg/ml in controls) and the active levels of TGF-b1 (14.2 pg/ml in XFS vs 4.9 pg/ml in controls) were significantly higher in XFS aqueous samples. In contrast, no difference was detected in the serum levels of TGF-b1 between XFS patients and controls. There was no difference in the aqueous levels of TGF-b2 and IGF-1 between XFS and controls. The concentration of these growth factors was correlated with total protein concentration in the same samples. No correlation could be established between protein concentration and the levels of the 3 growth factors measured. A significant correlation was found between age and protein concentration in XFS, but not in the controls. Since TGF-b1 induces the synthesis and accumulation of extracellular matrix, it is hypothesised that TGF-b1 plays an important role in the pathogenesis of XFS. Our data suggest that the increased levels of TGF-b1 are most likely due to enhanced local synthesis.