Eleven patients with intractable rheumatoid arthritis were treated with fractionated total lymphoid irradiation at a total dose of 20 Gy. Lasting improvement in clinical symptoms was found in four patients during treatment and the remaining patients experienced a similar benefit within 2 months of irradiation. There was marked reduction in exacerbations and the number of joints involved. Morning stiffness, joint swelling and tenderness decreased. Complications included severe fatigue during treatment and acute bacterial arthritis in multiple joints in one patient. Four of the patients have since died, one of renal failure and another of cardiogenic shock following surgery 3 and 24 months after total lymphoid irradiation. Both had generalised amyloidosis. The third patient developed joint empyema and died of toxic cardiac failure. The fourth died 3 months after resection of a Kaposi's sarcoma complicated by wound infection which responded to treatment. Immunologically, total lymphoid irradiation resulted in suppression of the absolute lymphocyte count and a reduction in T-helper cells, while the number of T-suppressor cells remained unchanged. These data provide evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis. Total lymphoid irradiation can induce sustained improvement in clinical disease activity, but severe, possibly fatal, side-effects cannot be ignored.