It has been shown that with increased carboxyhemoglobin (COHb) and associated decrease in blood oxygen-carrying capacity, a compensatory increase in brain-blood flow (BBF) develops. The BBF response in humans has been shown to be quite variable. Two experiments were conducted in which humans were exposed to sufficient carbon monoxide (CO) to produce COHb levels up to 18.4%. BBF was measured by the method of impedance plethysmography. The first was a pilot study in which BBF in 14 men was studied after transient exposure to various concentrations of CO in air. BBF increased as a function of COHb, but not to the same extent (or at all) in some subjects. In a confirmatory experiment with 12 men, BBF was measured once per hr during a four-hr experiment. All 12 subjects received CO. The variation of the BBF response among subjects was large and statistically significant while the variation over time was not significant. Thus it appears that the magnitude of the BBF response is unique for a given subject and differs across subjects. These results may help predict CO-induced behavioral decrements in future studies if subjects whose BBF response to COHb is small or absent are also more susceptible to impairment by acute CO exposure. (Copyright (c) 1992 Pergamon Press Ltd.)