The impact of meridional winds on the onset and evolution of equatorial spread F (ESF) is studied using the NRL ionosphere model SAMI3/ESF. The prevailing belief is that meridional winds have a stabilizing effect on the onset of ESF. In this letter, it is shown that this is not necessarily the case and that meridional winds can be destabilizing. We find that a wind profile with a positive gradient as a function of latitude (∂V m ∕ ∂θ ≥ 0) is a stabilizing influence on the generalized Rayleigh-Taylor instability; a wind profile with a negative gradient (∂V m ∕ ∂θ < 0) is a destabilizing influence. Here, a northward wind is positive, and θ increases in the northward direction. It is suggested that meridional wind profiles may account for, in part, the longitudinal and day-to-day variability of ESF.