Three patients with erythropoietic protoporphyria were treated with combined plasmapheresis and neocyte exchange transfusions that induced and maintained clinical and biochemical remissions. Red cell and plasma porphyrin levels normalized and patients developed a more normal tolerance to ultraviolet exposure. This treatment modality was an effective method of reversing other newly described abnormalities such as excessive erythropoiesis, abnormal RBC osmotic fragilities, elevated plasma viscosities, and hepatic and renal impairments.