Quasi-periodic variations in ionospheric F-region parameters associated with interplanetary magnetic field fluctuations have been reported by Huang et al. <2002>. Two mechanisms that could generate these ionospheric fluctuations are a time-varying electric field or neutral wind. We present simulation results of the response of the mid-latitude F-region ionosphere to these drivers using the NRL ionosphere model SAMI2. We obtain good agreement with Millstone Hill density and velocity observations for a zonal F-region electric field E ≃ ¿2.4 mV/m. We also obtain good agreement with density observations if the neutral wind fluctuates ~¿40 m/s along the geomagnetic field. However, this neutral wind variation corresponds to ~¿140 m/s in the meridional component of the horizontal neutral wind, and the fluctuating ion velocity is ~30% larger than those observed. This suggests that a fluctuating penetration electric field is probably responsible for the Millstone Hill observations.