To analyse the relationship of ultrastructural changes of glomerular basement membrane (GBM) and glomerular distributions of laminin alpha1 and laminin alpha5 in patients with Alport's syndrome.Twenty patients with Alport's syndrome were recruited. The thickness of GBM and the extension of thickening and splitting GBM were measured under transmission electron microscope. Normal renal tissues from 6 nephrectomies of renal carcinoma were taken as controls. Paraffin embedded sections of formalin-fixed renal tissue were processed for immunohistochemistry with monoclonal antibodies to laminin alpha1 and laminin alpha5. Their distributions in GBM were evaluated by a semiquantitative scale of positive extension: absent, 0; or =75%, 4.There were a variety of degrees of thickening or splitting GBM in patients with Alport's syndrome. Laminin alpha1 was positive in glomerular mesangial area and absolutely negative in GBM and laminin alpha5 was evenly positive in GBM in normal tissue. In Alport's syndrome, laminin alpha1 was much weaker in glomerular mesangial area, but strongly positive in GBM; laminin alpha5 in GBM was prominently reduced. There was a high negative correlation of semiquantitative scores between laminin alpha1 and laminin alpha5 (r=-0.83, P<0.001). The extension of thickening or splitting GBM was positively correlated with scores of laminin alpha1 in GBM (r=0.76, P<0.001; r=0.56, P=0.015), and was negatively correlated with scores of laminin alpha5 in GBM (r=-0.59, P=0.010; r=-0.53, P=0.025).Abnormal distribution of laminin alpha1 and laminin alpha5 in GBM is correlated with GBM thickening and splitting in human Alport's syndrome.