Ventilated piglets were studied to determine the effects of intravenous tolazoline infusions during hypoxia on the cerebral circulation and to assess whether cerebral responses reflect tolazoline-induced alterations in the systemic vasculature. We measured cerebral blood flow (CBF), cardiac output (CO), mean arterial pressure (MAP) and cerebral arteriovenous differences of O2 content during normoxia, isocapnic hypoxia (FiO2 14%), and hypoxia (FiO2 14%) with infusions of either saline (n = 7) or tolazoline (n = 10). Hypoxia alone resulted in comparable cardiovascular alterations in both groups. During hypoxia + saline MAP remained stable, but decreased during hypoxia + tolazoline, reflecting reductions in systemic vascular resistance (SVR) and variable changes in CO (reductions in 4 piglets, increases in 6). In both groups CBF rose during hypoxia alone and remained elevated during hypoxia with saline or tolazoline. Cerebral O2 delivery, extraction and uptake were unchanged in both groups. Although mean CBF was similar during hypoxia with saline or tolazoline, CBF was variable during tolazoline, decreasing in 4 of 10 piglets; CBF never fell with saline. Tolazoline-induced changes in MAP correlated with CBF (r = 0.90, P less than 0.001) emphasizing the importance of MAP in maintaining CBF during hypoxia. Importantly, decreases in CBF also paralleled falls in CO. In the presence of a pressure-passive cerebral vasculature, the adequacy of increases in CO to offset tolazoline-induced reductions in SVR determines MAP and ultimately CBF. Thus, cerebral vascular responses to tolazoline infusions during hypoxia reflect tolazoline-induced systemic circulatory derangements.