Exercise performed after exposure to various pneumoedematogenic gases can increase the severity of pulmonary edema beyond that which occurs when exposure is followed by rest. The present study was performed to investigate the potential relationship between a preexisting breach in the lung's permeability status following exposure to an edematogenic gas (perfluoroisobutylene, PFIB) and the potentiating effects of postexposure exercise. Rats were exposed to a concentration of PFIB (100 mg/M3 for 10 min) that results in a unique postexposure latency period (approximately 8 h) prior to the occurrence of overt pulmonary edema. The study examined how exercise performed during and after the latency period affects the severity of the injurious response to this toxic gas. The initial results indicated that exercise performed during the post-PFIB exposure latency period does not potentiate the injurious response, as judged by conventional lung gravimetric and histopathological criteria, but when overt pulmonary edema was preexistent, exercise had a potentiating effect. Changes in lavageable protein were assessed as a more sensitive indicator of permeability changes that may occur during the latency period following PFIB exposure, and the study examined how exercise performed early during the latency period affects this index of pulmonary edema. The study also assessed whether PFIB-induced damage to lung cells is enhanced by exercise during the latency period by measuring lavageable lactate dehydrogenase activity. The results from these latter experiments suggest that a preexisting enhancement in lung permeability is not an absolute requirement for exercise to potentiate the pulmonary edematous response in lungs that are undergoing insidious injury, and that postexposure exercise does not enhance the cell-killing effects of PFIB as a mechanism underlying the exercise potentiating response. Conceivably, the ability of exercise to increase lavageable protein in the absence of a preexisting increase in lung permeability may be due to hyperventilation- and/or pulmonary hypertension-associated intercellular junctional changes that may occur during exercise. Additionally, it remains possible that exercise during PFIB-induced insideous lung injury results in an enhancement in the rate of transcellular transport of blood proteins onto the alveolar surface.