A variety of diseases, sharing only hypergammaglobulinemia in common, are associated with impaired urinary-concentrating ability and with impaired urinary acidification after acid-loading. Forty-seven patients with leprosy were studied to determine whether or not elevated concentrations of serum globulins are related causally to abnormal distal renal tubular function. In nine patients, urinary pH did not decrease appropriately in response to NH4Cl. Two of these patients and five more without defective acidification were unable to adequately concentrate the urine after water deprivation and vasopressin administration. These defects were unrelated to the type of leprosy, to the concentrations of serum globulins or individual immunoglobulins, to the presence of rheumatoid factor or cryoglobulins, or to the administration of diaminodiphenylsulfone. Renal biopsy specimens from six patients with impaired urinary acidification and/or concentration showed no interstitial inflammatory cell infiltrates or other abnormalities. Impaired distal renal tubular function in patients with leprosy may be another of the nonspecific immunologic abnormalities that have been encountered in patients with this disease.