Numerous behavioral and environmental factors modulate the production of new cells in the adult mammalian brain. Although sleep loss has previously been shown to dramatically suppress brain cell proliferation, the effect of recovery sleep after a period of sleep deprivation is not known. Using the disk-over-water paradigm, adult male Sprague-Dawley rats were sleep deprived for 48 h. Separate groups were then allowed either an 8 h period of recovery sleep or an additional 8 h of sleep deprivation. A third group of rats served as a control, and were not sleep deprived. At 54 h, all rats received an injection of 5-bromo-2'-deoxyuridine (200 mg/kg, i.p.) and were killed 2 h later. When compared with control rats, a 36% reduction in cell proliferation was observed in the dentate gyrus of rats subjected to 56 h of sleep deprivation. A similar reduction in proliferation (39%) was observed in rats allowed an 8 h period of recovery sleep. In both deprivation groups, the magnitude of suppression of cell proliferation was approximately twice as large in the posterior hippocampus as it was in the anterior hippocampus. These data confirm previous results that an extended period of sleep deprivation exerts a strong suppressant effect on cell proliferation in the rat dentate gyrus, and demonstrate that this suppression of cell proliferation shows no evidence of recovery for at least 8 h following a 48 h period of sleep deprivation.