Recently, several high-impact reviews suggest that regular aerobic exercise is beneficial for maintaining cognitive function in aging adults. Higher cerebral blood flow and/or cerebrovascular reactivity may explain the favorable effect of exercise on cognition. In addition, prostaglandin-mediated vasodilator responses may be influenced by regular exercise. Therefore, our purpose was to evaluate middle cerebral artery (MCA) vasodilator responses in healthy adults before and after cyclooxygenase inhibition. A total of 16 young (26 ± 6 yr; 8 males, 8 females) and 13 older (64 ± 6 yr; 7 males, 6 females) healthy adults participated in the study. Aerobic fitness was determined by maximal aerobic capacity (Vo2max) on a cycle ergometer. MCA velocity (MCAv) was measured at baseline and during stepped hypercapnia (2%, 4%, and 6% FiCO2) before and after cyclooxygenase inhibition using indomethacin. To account for differences in blood pressure, cerebrovascular conductance index (CVCi) was calculated as MCAv/mean arterial pressure. Cerebrovascular reactivity slopes were calculated from the correlation between either MCAv or CVCi and end-tidal CO2. Young adults demonstrated greater MCAv reactivity (1.61 ± 0.17 vs. 1.06 ± 0.15 cm·s(-1)·mmHg(-1); P < 0.05) and CVCi reactivity (0.015 ± 0.002 vs. 0.007 ± 0.002 cm·s(-1)·mmHg(-1); P < 0.05) compared with the older adults. There was no association between cerebrovascular reactivity and Vo2max in the combined group of subjects; however, in older adults MCAv reactivity was correlated with maximal aerobic fitness (r = 0.64; P < 0.05). Furthermore, the change in MCAv reactivity (between baseline and indomethacin trials) was also associated with Vo2max (r = 0.59; P < 0.05) in older adults. Cerebral vasodilator responses to hypercapnia were associated with maximal aerobic capacity in healthy older adults. These results may explain the physiological link between regular aerobic exercise and improved cognitive function in aging adults.