Studies were initiated 10–12 yr ago to determine the biological effects of inhaled plutonium. Sixty-five beagle dogs inhaled 239PuO2 and were held for life-span observations. Sixty dogs died or were euthanized when death was imminent due to plutonium-induced pulmonary fibrosis and/or neoplasia 2–135 months postexposure. Twenty-four of the dogs had primary pulmonary neoplasia, including 20 of the 21 dogs that survived at least 4.5 yr post-exposure. Most lung tumors were bronehiolo-alveolar carcinomas of peripheral origin with metastases to several other tissues. Two squamous cell carcinomas, three epidermoid carcinomas and three thoracic sarcomas were also observed. The estimated initial alveolar deposition in the dogs with plutonium-induced tumors ranged from 0.2 to 3.3 μCi. Approximately 10% of the alveolar-deposited plutonium was retained in the lungs after 8–10 yr postexposure, with an accumulated average radiation dose to the lungs of 2000 to 12,000 rads in the tumor-bearing dogs. Forty to fifty per cent of the plutonium was translocated to the tracheobronchial and mediastinal lymph nodes, 10–15 % to the liver, 5 % to the skeleton and 5% to the abdominal lymph nodes. The highest plutonium concentrations occurred in the tracheobronchial, mediastinal and abdominal lymph nodes, followed in descending order by lungs, liver and skeleton. Respiratory insufficiency and lymphopenia were the primary clinical signs associated with the fibrotic, metaplastic and neoplastic changes in the lungs, and with the fibrosis of the lymph nodes. The pathology in these tissues may have influenced the clearance and translocation rates of the plutonium. Alveolar deposition of more than about 1 nCi/g of lung, about 30 times the quantity, at equilibrium, resulting in an average lung dose of 0.3 rem/week, might be expected to cause premature death due to pulmonary pathology. Experiments were initiated in 1970 to study dose-efrect relationships at low dose levels in 200 dogs depositing 0.002–3.0 μCi of 239PuO2 or 238PuO2. The lowest level corresponds to an average lung dose of 0.3 rem/week. This study should further identify the critical tissues for inhaled plutonium at low dose levels.