The functions of membrane bound proteins are regulated by the physical properties of the cell membrane. Lymphocyte dysfunction in IgA nephropathy may therefore be related to abnormal cell membrane fluidity. In this study we have examined peripheral blood mononuclear cell membrane fluidity and the expression of HLA antigens on the surface of lymphocytes in IgA nephropathy subjects compared to normal controls and disease controls. Twenty-two IgA nephropathy subjects with normal or mildly elevated serum creatinine (serum creatinine Fluorescence anisotropy for diphenylhexatriene of mononuclear cells from IgA nephropathy subjects was significantly lower compared to mononuclear cells from normal control subjects and disease control subjects, indicating higher membrane fluidity (median values, IgA nephropathy 0.161; normal control 0.175; disease control 0.175; P<0.001 and P<0.001). Fluorescence anisotropy for trimethylammonium-DPH was lower in the IgA nephropathy groups compared to the normal control group (median values, IgA nephropathy 0.268; normal control 0.274; P<0.001), but not significantly different compared to the disease control group (0.272). HLA class I expression on the surface of B lymphocytes was significantly higher in the IgA nephropathy group compared to the normal control and disease control groups (median values, IgA nephropathy 30364, normal control 15495; disease control 16907; P=0.0001 and P=0.002 respectively). This study provides evidence of abnormal cell membrane architecture and increased HLA class I expression in Iga nephropathy.