Changes in spontaneous activity within the cortex recognized by subthreshold fluctuations of the membrane potential of cortical neurons modified the response of cortical neurons to sensory stimuli. Sensory stimuli occurring in the hyperpolarized "down" state evoked a larger depolarization and were more effective in evoking action potentials than stimuli occurring in the depolarized "up" state. Direct electrical stimulation of the thalamus showed the same dependence on the cell's state at the time of the stimulus, ruling out a strictly thalamic mechanism. Stimuli were more effective at triggering action potentials in the down state even during moderate de- or hyperpolarization of the somatic membrane potential. The postsynaptic potential (PSP) evoked from the down state was larger than the up state PSP but achieved about the same peak membrane potential, which was also near the reversal potential of the PSP (about -51 mV). Chloride loading shifted the reversal potentials of both the up state and the whisker-evoked PSP toward a more depolarized membrane potential. In addition, the threshold for action potentials evoked from the down state was lower than for spikes evoked in the up state. Thus the larger PSP from the down state may be caused by its larger driving force, and the state dependence of action potential generation in response to whisker stimulation may in part be related to a shift in threshold. Different mechanisms are therefore responsible for the state-dependence of PSP amplitude and the spike frequency response to the whisker stimulus.