The effects of the application of positive end expiratory pressure (PEEP) ventilation, with and without body counterpressure (CP), on circulating prostaglandin-like substances (PGL) were studied in chloralose anesthetized dogs. The normal respiratory movements were paralysed with succinylcholine chloride. Arterial levels of PGL were continuously bioassayed using Vane's blood superfusion method. PEEPs of 10 and 20 mm Hg elicited PEEP-related increases in functional residual capacity and circulating PGL levels and decreases in blood pressure, left ventricular dP/dt, and heart rate. The PGL appeared to be PGE or prostacyclin in character. When PEEP and CP were simultaneously applied, the increments or decrements of indices described above were reduced. It is concluded that increases in the levels of circulating PGL are attributable, at least in part, to hyperexpansion of the lungs during PEEP and that some of the cardiovascular deterioration observed during and after PEEP may be the result of the vasodilating and cardiodepressing effects of PGL.