Because arousal plays a critical role in activation of epileptic phenomena, we analyzed the behavior of interictal generalized spike-and-waves (S-W) during the two recently identified modalities of arousal control during NREM sleep: (a) the cyclic alternating pattern (CAP), expressed by successive biphasic (phase A and phase B) fluctuations of arousal; and (b) non-CAP (NCAP), characterized by prolonged stable periods of EEG and arousal level. Within the single NREM stages, phase A consists of clusters of phasic events associated with transient arousal activation, whereas phase B is represented by the periodic reappearance of the EEG background and reflects a rebound inhibitory condition. The polysomnograms of 10 subjects with a wide age range and affected by primary generalized epilepsy displayed significant differences (all at p less than 0.01) between the spike indexes (S-W/min) of CAP (2.9) and NCAP (1.3), of phase A (7.4) and phase B (0.3), and of NCAP and phase B. For distribution of S-W, a significant prevalence of EEG paroxysms was detected during CAP as compared with NCAP (68 vs. 32%, p less than 0.001), and 93% of all the interictal bursts that occurred in CAP occurred in phase A (p less than 0.001). Our data stress the arousal-dependent influence of CAP and NCAP on modulation of generalized epileptic mechanisms during sleep.