To elucidate the relationship between localization of β2-microglobulin (β2-MG) and renal lesions or dysfunction, 119 patients with various renal diseases and various degrees of renal injuries were examined: patients with β2-MG deposition (group 1, n = 69), and patients without renal β2-MG deposition (group 2, n = 50). β2-MG was found mainly in the tubular epithelium and tubular casts. No significant difference in the degree of proteinuria and hematuria were found between the two groups. Group 1 had a significant decrease in glomerular filtration rate (GFR; p < 0.01): the average values of GFR in group 1 and 2 were 61.1 ± 35.7 and 95.4 ± 34.5 ml/min. Group 1 had a significant decrease in the phenolsulfonphthalein excretion test (p < 0.01) and the maximum urine specific gravity in Fishberg’s concentration test (p < 0.02). Group 1 had a significant high incidence of glomerular sclerotic lesions (p < 0.001), arteriolar elastosis (p < 0.01), tubulo-interstitial changes (p < 0.001) and renal deposition of lysozyme (p < 0.001). The present study demonstrates that the immunohistological study of renal β2-MG deposition is a reliable method to identify renal dysfunction and renal injuries, especially the presence of tubulo-interstitial changes, in various renal