1. The effects were investigated of non-dialysable substances obtained from urines of patients with nephrotic syndrome and those with myelomatosis (heavily laden with light chains) on renal function in a system in vitro. 2. The ability of the rat kidney slice to accumulate hippurate and tetraethylammonium (TEA), and to produce ammonia and glucose, was measured after incubation in urine proteins from ten patients with myelomatosis. All slice functions measured at protein concentrations of 10 mg/ml decreased significantly compared with control. Hippurate accumulation averaged 58%, TEA accumulation, 53%, ammoniagenesis, 59%, and gluconeogenesis, 57% of control. An inverse relationship between protein concentration and hippurate accumulation was noted. 3. Slices incubated in proteins from eight nephrotic patients showed no consistent decrease from control in hippurate accumulation (95%), TEA accumulation (103%), ammoniagenesis (91%) or gluconeogenesis (92%). 4. Since urinary proteins from patients with myelomatosis, unlike urinary proteins from the nephrotic patients, had a consistently deleterious effect on the function of renal slices, this suggests that proteins found in urines from myelomatous patients may play a role in the disturbance of proximal tubular function sometimes seen in this disorder.