The microscopic appearance of lungs subjected to six hours of conventional ventilation (CV), standard high frequency jet ventilation (HFJV), and HFJV combined with low rate intermittent mandatory ventilation (CHFJV) was studied in 22 mongrel puppies. A lung injury model was created by insufflating 4 ml/kg of a 20% mixture of meconium into the trachea. The animals were initially ventilated at the same mean airway pressure (Paw). Subsequently, if PCO2 fell below 20 torr, peak and mean airway pressures were reduced. A scoring system was devised which assigned 0-3 points for each of eight lung injury parameters, and a total lung injury score (TLIS) was calculated. CHFJV resulted in significantly less bronchopneumonia and edema, when compared to CV. A consistent, though not significant, trend toward lesser injury scores in CHFJV animals was noted for several other parameters. Six of eight lungs exposed to CV had TLIS greater than 5 compared to only 1 of 9 ventilated by CHFJV. (P = 0.02). It is concluded that CHFJV may have a protective effect on the lung, perhaps because effective gas exchange is achieved with a lower pressure amplitude and at lower Paw.