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Serum levels, urinary excretion, and clearances of several proteins of different molecular weights were studied in 18 patients with mono- and myelomonocytic leukemia. Nine patients had normal renal function (group A) and nine had impaired renal function with azotemia (group B). The majority of patients in both groups had increased concentration of immunoglobulins, particularly IgG, IgA, and IgM; IgD level was normal. Serum transferrin and α2-macroglobulin were frequently reduced while the level of ceruloplasmin was often increased, especially in patients with azotemia. The activity of lysozyme in the serum was high in all patients, but was considerably higher in group B. Proteinuria was found in most patients but was more prominent in group B. Almost invariably albumin constituted less than 25% of the total protein excreted. Qualitative analysis of various urinary proteins by immunochemical techniques and clearance studies suggested the presence of glomerular as well as tubular dysfunction. Determination of urinary lysozyme frequently showed no direct correlation between the serum level of the enzyme and its concentration in the urine or its clearance by the kidney. In addition to glomerular filtration, impaired tubular reabsorption may account for the high level of lysozyme in the urine. It is postulated that the very high level of lysozyme in the glomerular filtrate and possibly hypergammaglobulinemia may play a role in the induction of tubular damage. Renal impairment has been correlated with histological changes in the kidneys. From a comparative study of various leukemias, it seems that the combined glomerular-tubular dysfunction is a manifestation unique to mono- and myelomonocytic leukemia.