Criteria were defined for recognizing 29 patients with a localized plasmacytoma of bone and 20 patients with an indolent variety of multiple myeloma in order to justify long-term follow-up without chemotherapy. All patients with indolent myeloma were asymptomatic from their low tumor mass disease, had a hemoglobin greater than 10 g/dl, and showed no more than 3 lytic bone lesions. The presence of more than 200 mg/day of Bence Jones protein was usually followed by disease progression within 2 yr. Serial assessments of myeloma protein level provided a useful index of changing tumor load and the need for chemotherapy. In patients with localized disease, radiotherapy usually reduced myeloma proteins markedly with subsequent disease control for many years, even though small serum peaks persisted. Chemotherapy for multiple myeloma was not required for a median of 8 yr in patients presenting with localized disease and of 3 yr in those with indolent myeloma. The additional survival from the start of drug treatment was similar to that of comparable patients treated promptly for overt multiple myeloma. The delay of chemotherapy until evidence of tumor progression did not affect the long-term outcome of patients with localized or indolent myeloma.