The production of monodisperse human albumin millimicrospheres (diameter less than 1 micron) and labeling with 99mTc 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 81mKr (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 81mKr or 127Xe 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 81mKr images was found in all patients studied. For same-day ventilation/perfusion studies, labeling of the millimicrospheres with 111In yielded images of comparable quality to those obtained with the 99mTc-labeled aerosol.