We characterized middle cerebral artery (MCA) blood flow velocity waveforms measured by transcranial Doppler ultrasonography in premenopausal (26.6 +/- 6.1 years, mean +/- SD) and postmenopausal (54.0 +/- 3.6 years) women, of whom six were receiving hormone therapy (PM-HT) and seven were not (PM-non-HT). We hypothesized that feature points on MCA waveforms are altered in postmenopausal women compared with those in young women. A short protocol involved maintaining end-tidal PO2 at euoxia (88 mm Hg) and end-tidal PCO2 at 1.5 mm Hg above eucapnic values using a dynamic end-tidal forcing system. Doppler data for the velocity spectral outline (Vp) were collected every 10 ms, and velocity waveform analyses were done on a beat-by-beat basis. Waveform features were identified over each cardiac cycle, including the average Vp (VCYC), maximum acceleration (AMAX), and the ratio of the velocity at the reflected wave and the velocity at peak systole (VR:VMAX). VCYC was unchanged between premenopausal and postmenopausal women (69.4 +/- 9.6 and 67.5 +/- 11.1 cm/s, respectively). AMAX was significantly higher (P = 0.007) in premenopausal women (987.9 +/- 280.7 cm/s) compared with postmenopausal women (743.1 +/- 100.3). Conversely, VR:VMAX was significantly smaller (P < 0.001) in premenopausal women (0.90 +/- 0.09) compared with postmenopausal women (1.11 +/- 0.05). In postmenopausal women, the reflected wave is higher than the maximum velocity at peak systole, suggesting the presence of a shoulder in the MCA waveform. Further investigations are required to assess whether this waveform analysis can provide insight into pathophysiologic changes in cerebral hemodynamics with aging.