Summary1. The most specific change observed in the kidney of patients dying from multiple myeloma is tubular obstruction by dense hyaline casts, frequently leading to lesions of the tubular cells. This type of nephropathy is not accompanied by optically discernible changes within the glomeruli.2. In 8 % of myelomatous patients with uremia, renal failure is secondary to the deposition of paramyloid substance in glomerular capillaries. This type of renal lesion is not constantly accompanied by similar changes within other organs.3. Although of frequent occurrence, hypercalcaemia is a rare cause of renal failure in multiple myeloma. It constitutes probably a late event in the disease.4. There is a remarkable correlation between Bence-Jones proteinuria, specific casts and renal failure. This group of signs is frequently observed in myelomatous patients who do not show alterations in gamma-globulin fraction by paper electrophoresis. It is thus obvious that renal failure is linked to the production of abnormal globulins of low molecular weight which can cross the glomerular barrier and constitute obstructive casts within the tubular lumen.5. The abnormal serum globulins with molecular weight similar to that of normal globulins cannot leak through the glomeruli. It follows that they have no nephrotoxic properties.6. The production of abnormal globulins of low molecular weight (Bence-Jones protein) is most frequent and most active in cases where synthesis of globulins with higher molecular weight is not increased.7. Indeed, studies using tagged amino-acids have shown that urinary globulins of low molecular weight are not produced by the breakdown of abnormal serum globulins of higher molecular weight.