The responsiveness of cortical neurons is strongly and rapidly influenced by changes in the level of local network activity. In rodent somatosensory cortex, increases in network activity increase neuronal responsiveness to the intracellular injection of brief conductance stimuli but paradoxically decrease responsiveness to brief whisker deflections. However, whisker stimulation frequently evokes long-lasting changes in the level of local circuit activity. The ability of stimuli to successfully evoke prolonged increases in circuit activity is associated with both an increase in the amount of conductance evoked by a whisker stimulus and an increase in action potential responsiveness to whisker stimulation. In addition, brief whisker stimuli presented during periods of high network activity evoke postsynaptic potentials containing a greater proportion of inhibition, consistent with an increased efficiency in the activation of inhibitory mechanisms during the Up state. In contrast, during prolonged and variable whisker stimulation, increased network activity is associated with an increase in overall responsiveness, dynamic range, output gain, and correlation between action potential response and speed of whisker movement. We conclude that stimulus-evoked or spontaneous alterations in cortical state can influence neuronal responsiveness in a complex manner, resulting in large changes in which, and how, sensory stimuli are represented.