The responses of pial arterioles to changes in PaCO2 were studied in anesthetized cats equipped with cranial windows for the observation of the pial microcirculation. The percentile increase in vessel caliber induced by hypercapnia was size dependent, with the smaller vessels responding more vigorously than the larger ones. In contrast, the vasoconstrictor responses to arterial hypocapnia were size independent. Following topical application of phentolamine (10(-5) M), or after ipsilateral extirpation of the superior cervical ganglion, the increase in arteriolar caliber caused by moderate hypercapnia (5% CO2 inhalation) in the larger arterioles (greater than 100 micron in diameter) increased and became equal to that of the smaller arterioles (less than 100 micron in diameter). The response to hypocapnia was not affected by phentolamine. The results indicate that a major reason for the greater responsiveness of smaller vessels to moderate hypercapnia is the fact that the response of the larger vessels is limited by neurogenic vasoconstriction resulting from increased activity of adrenergic nerves originating from the cervical sympathetic chain. The absence of an influence of the sympathetic nervous system on the responses to hypocapnia is explained by the lack of significant resting neurogenic vasoconstrictor tone in pial arterioles of anesthetized cats.