The effect was evaluated in puppies and adult dogs by measuring the rate of passage of radioactive iodinated human serum albumin from plasma into the cerebrospinal fluid and by determining the plasma and cerebrospinal fluid glutamic oxalacetic transaminase and lactic dehydrogenase activities. Arterial O2 concentration and saturation, CO2, and pH determinations were obtained. In puppies, hypercapnia was associated with marked respiratory acidosis and produced a great increase in the rate of transfer of albumin I131 from plasma to cerebrospinal fluid. Prolonged hypoxia also produced a definite increase in permeability of the blood-cerebrospinal fluid barrier. Increased concentration ratios of cerebrospinal fluid enzyme activity/plasma enzyme activity were observed in both groups. Hypoxia alone did not cause significant changes. In adult dogs, hypercapnia or hypoxia did not result in comparable findings.