The spiral arteries of the human uterus are considerably remodeled structurally during pregnancy to facilitate an increase in blood flow. An immunohisto-chemical study was undertaken to determine whether the spiral arteries were innervated and, if so, whether they were denervated in the process of the physiologic vascular changes of normal pregnancy or, conversely, remained innervated in the absence of physiologic changes in abnormal pregnancy. Uterine tissues from nonpregnant nulliparous women, from normal early pregnancy, from normal late pregnancy, from abnormal early pregnancy (i.e. spontaneous abortions), and from abnormal late pregnancy (i.e. preeclampsia and intra-uterine growth retardation) were subjected to immunohistochemistry using a panel of neuron-associated antibodies (neurofilament, neuron-specific enolase, S100 protein, protein gene product 9.5). All sections of the nonpregnant uterus showed an abundance of nerves deep in the myometrium, some of which were associated with radial and arcuate arteries. Very few nerves were demonstrated at the endomyometrial junction and no nerves were seen accompanying the intramyometrial spiral arteries. In both normal and abnormal pregnancy, nerves were not detected in the decidua or accompanying intradecidual spiral arteries, whether they were physiologically altered or not. Nerves were seen in the myometrium in 7 of 10 normal and in 1 of the 8 third-trimester abnormal placental beds, but none were seen accompanying intramyometrial spiral arteries, whether showing physiological changes or not. The lack of innervation of the spiral arteries in the nonpregnant state as well as in normal and abnormal pregnancy suggests that nonneurogenic mechanisms control blood flow at the spiral-arterial level.