Elevated intrathoracic pressure due to positive end-expiratory pressure (PEEP) has the potential for increasing intracranial pressure (ICP) and reducing arterial blood pressure (HP). Such changes could critically reduce cerebral perfusion pressure (CPP = BP – ICP). This possibility was investigated in 15 cats with artificially-produced expanding intracranial masses (intracranial balloon). The interrelationships among ICP and central venous and arterial pressures were observed during application and removal of graded levels of PEEP (5, 10, 15 cm H2O). The electroencephalogram and pupillary diameters were monitored. At various levels of ICP, nine of the cats were given oleic acid intravenously to embolize the lung and cause pulmonary dysfunction.In cats not given oleic acid, PEEP caused a maximal reduction in cerebral perfusion pressure of 45 ± 4 torr(SEM), accompanied by variable changes in 1CP. PEEP application in the absence of oleic acid embolization of the lungs caused electroencephalographic abnormalities in 77 per cent of these cats, while pupillary diameters increased in 56 per cent. Animals embolized with oleic acid had significantly less (P< .001) severe CPP reductions (mean 21 ± 4 torr) than did the non-embolized animals, and developed no EEG change due to PEEP. However, increases in pupillary diameter still occurred in 33 per cent of cats given oleic acid when PEEP was applied.In 82 per cent of the PEEP applications (n = 44) in both experimental groups only insignificant increases in intracranial tension occurred (average peak ICP gain < 1.5 torr). Abrupt increases in ICP exceeding 11 torr (15 cm H2O) occurred in four animals in each group. This happened most frequently (63 per cent) when the intracranial tension before PEEP was above 15 torr. Sudden removal of or reduction in PEEP was accompanied by increases in arterial and intracranial pressures in both groups, although this response was attenuated in the cuts given oleic acid.The results indicate a potential for PEEP to evoke neurologic complications in patients who have intracranial disease and that the presence of pulmonary disease may attenuate these deleterious side effects. Monitoring of neurologic function as well as blood-gas and cardiovascular effects of PEEP in patients who have intracranial disease is suggested.