The slow wave is a fundamental cortical rhythm that emerges in deep non rapid eye movement sleep. It is thought to underlie essential restorative processes and facilitate the consolidation of declarative memories. Animal studies show that slow wave activity is composed of rhythmically recurring phases of widespread, increased cortical cellular and synaptic activity, referred to as active- or up-state, followed by cellular and synaptic inactivation, referred to as silent- or down-state. However, its neural mechanisms in humans are poorly understood. To elucidate the intracortical neuronal mechanisms of slow wave activity in humans, laminar microelectrodes were chronically implanted into the cortex of patients with focal epilepsy undergoing cortical mapping for seizure focus localization. We found that slow wave activity in humans reflects a rhythmic oscillation between widespread cortical activation and silence. Cortical activation was demonstrated as increased wideband spectral power including virtually all bands of cortical oscillations, increased multiple and single unit activity, and powerful inward trans-membrane currents, mainly localized to the supragranular layers. Neuronal firing in the up-state was sparse and the average discharge rate of single cells was less than expected from animal studies. Action potentials at up-state onset were closely synchronized across all cortical layers, suggesting that any layer could initiate firing at up-state onset. These findings provide experimental evidence that slow wave activity in humans is characterized by hyperpolarizing currents associated with suppressed cell firing, alternating with high levels of oscillatory synaptic/trans-membrane activity associated with increased cell firing. Our finding that slow wave activity and corresponding high frequency rhythms including spindle, alpha, beta, gamma and ripple oscillations mainly involve supragranular layers is consistent with the massive cortical expansion of neuronal number and increased apical dendritic complexity observed in humans. The strong supragranular oscillatory activity in sleep may be beneficial for the local, higher order processing of previous sensory experience, since these layers are interconnected by dense cortico-cortical projections forming fine-scale functional networks to perform integrative functions. The weaker infragranular activity may reflect the relatively suppressed cortical executive, output functions, which may prevent effective connectivity between distant cortical areas from developing in slow wave sleep.