At present, there is no sensitive and specific test to confirm the clinical impression that a respiratory disorder is due to aspiration of gastric contents. Since intravenous technetium pertechnetate (99mTcO4-) has been shown to be safe, actively concentrated in the gastrointestinal tract, and secreted into gastric juice, we sought to determine whether 99mTcO4-, when given intravenously, is suitable to detect pulmonary aspiration of small amounts of gastric contents in rabbits. Biodistribution studies over 24 h revealed that 99mTcO4- persistently appeared in the stomach, thyroid, and salivary glands and did not appear in the lungs. Pharmacokinetic studies showed that 99mTcO4- was rapidly picked up by the stomach wall and secreted promptly into the stomach lumen and that the stomach wall persistently secreted 99mTcO4- into stomach contents for 24 h. By injecting 99mTcO4- through an intratracheal catheter in order to simulate aspiration, the radioactive threshold for imaging intrapulmonary 99mTcO4- was determined to range between less than 0.5 microCi and 2 microCi, depending on the amount of background activity in the blood pool. By measuring the radioactivity in stomach contents (microCi/g), over 24 h after intravenous injection of 2 mCi of 99mTcO4-, we were able to calculate the amount of aspirated stomach contents that our technique should reveal at various time points. We concluded from this preliminary feasibility study that 99mTcO4-, when given intravenously, is suitable to detect pulmonary aspiration of small amounts (less than or equal to 4 ml for 8 h after an intravenous dose of 2 mCi) of gastric contents in human patients. Since our biodistribution studies show that saliva as well as stomach contents are potential sources for any aspirated 99mTcO4-, how to distinguish aspiration of oropharyngeal from stomach contents remains to be determined. It also remains to be determined how long 99mTcO4- remains in the lungs after it has been instilled; clearance that is too rapid significantly decreases the ability of this agent to reveal aspiration.