The effects of chemotherapy were evaluated in 43 multiple myeloma patients with high monoclonal globulin levels in both serum and urine. In responding patients, Bence Jones protein excretion declined more rapidly and markedly than the serum myeloma protein. Bence Jones protein excretion was reduced by 50% within 2 mo in responders, remained unchanged in nonresponders, and declined with a slow halving time of 2–7 mo in patients with partial disease control. Three patients with clinical resistance to treatment showed atypical protein changes and progressively more Bence Jones protein excretion relative to their serum monoclonal component. Serial measurements of Bence Jones protein excretion provided an early and reliable index of tumor mass change in patients with multiple myeloma.