We present a patient with a history of heroin addiction and 19 years of methadone maintenance who died of respiratory failure following nine years of slowly progressive dyspnea. During this nine-year period, chest X-rays consistently had revealed large, bilateral densities having the appearance of progressive massive fibrosis (PMF). At autopsy the lungs exhibited corresponding areas of dense, gritty consolidation, which microscopically showed an active granulomatous reaction with associated vascular obliteration. Throughout the lesions were refractile and birefringent plates of particulate material. Interstitial, perivascular, and vascular granulomas also were noted in the periphery of the lung. X-ray energy spectroscopy and diffraction studies of the particulates confirmed the presence of talc at levels of 540 x 106 particles/g of dried tissue in the mass lesion and 96 x 106/g in the peripheral lung. Smaller numbers of silica particles also were identified. Approximately 30% of the talc particles were greater than 5 μ in maximum dimension, a finding consistent with intravenous delivery. Particles larger than 15 μ were only found in the mass lesion. We conclude that massive granulomatous lesions with the radiographic appearance of PMF can occur in association with intravenous injection of talc. We suggest that particle size and cumulative particle load are important in the pathogenesis of the lesions.