The production of monodisperse human albumin millimicrospheres (diameter 1 ..mu..m) and labeling with /sup 99m/Tc is described. A system constructed to nebulize and deliver a dry aerosol yielded a lung delivery efficiency of approximately 25%. In 48 patients without and with varying degrees of chronic obstructive lung disease, quantitative comparison with /sup 81m/Kr (penetration index, regional distribution of activity in the lungs) demonstrated similar penetration of the particles to the lung periphery (r = 0.89 and r = 0.94, respectively). Qualitative comparison with /sup 81m/Kr or /sup 127/Xe showed complete or a high degree of diagnostic agreement in all but one patient. Semiquantitative scoring of hot spots as a substrate of local turbulent airflow showed a close inverse correlation (r = -0.82) with the forced expiratory volume in 1 s (FEV 1.0%), thus providing additional information about the severity of the airway obstruction. In 24 patients with suspected pulmonary embolism, complete agreement between aerosol and /sup 81m/Kr images was found in all patients studied. For same-day ventilation/perfusion studies, labeling of the millimicrospheres with /sup 111/In yielded images of comparable quality to those obtained with the /sup 99m/Tc-labeled aerosol.