Nine patients with mixed cryoglobulinemia and severe membranoproliferative glomerulonephritis were treated with plasma exchange alone or in combination with medium to low amounts of corticosteroids, but never with cytotoxic drugs. In 5 patients renal function and/or proteinuria improved after plasma exchange, and no clinical relapse usually occurred when the procedures were reduced or discontinued. These procedures seemed of particular effect in the presence of histologically active and not irreversible lesions and rapid deterioration of renal function. While cryocrit almost invariably decreased, circulating immune complex or complement levels were unpredictably affected by plasma exchange. Cryocrit, but not immune complex or complement levels, was the serological parameter which most often closely correlated with signs of renal involvement (i.e., proteinuria and/or serum creatinine). Thus, plasma exchange might be a safe and useful tool in the treatment of an often drug-resistant and rapidly progressive renal involvement occurring in patients with mixed cryoglobulinemia.