We have shown recently that development from neonatal to adult life affects cerebrovascular tone of mouse cerebral arteries through endothelium-derived vasodilatory mechanisms. The current study tested the hypothesis that development from fetal to adult life affects cerebral artery vascular smooth muscle (VSM) [Ca²⁺]_i sensitivity and tone through mechanism partially dependent upon endothelium-dependent signaling. In pressurized resistance sized cerebral arteries (150µm) from preterm (95 d gestation) and near-term (140 d gestation) fetuses, and nonpregnant adult, we measured vascular diameter (µm) and [Ca²⁺]_i (nM) as a function of intravascular pressure. We repeated these studies in the presence of inhibition of NOS (L-NAME), COX (Indomethacin) and endothelium removal (E-). Cerebrovasculature tone (E+) was greater in arteries from 95d fetuses and adult compared to 140d sheep. Ca²⁺ sensitivity was similar in 95d fetus and adult, but much lower in 140d fetus. Removal of endothelium resulted in a reduction in lumen diameters as a function of pressure (greater tone) in all treatment groups. [Ca²⁺]_i sensitivity difference among groups were magnified after E-. NOS inhibition decreased diameter as a function of pressure in each age group, with significant increase in [Ca²⁺]_i to pressure ratio only in the 140d fetus. Indomethacin increased tone and increased [Ca²⁺]_i in the 140d fetus, but not the other age groups. Development from near-term to adulthood uncovered an interaction between NOS- and COX-sensitive substances that functioned to modulate artery diameter but not [Ca²⁺]_i. This study suggests that development is associated with significant alterations in cerebral VSM, endothelium, NOS, and COX responses to intravascular pressure. We speculate that these changes have important implications in the regulation of cerebral blood flow in the developing organism.