The endogenous neurosteroid allopregnanolone has recently been demonstrated to have somnogenic properties that are very similar to those of other agonistic modulators of GABA(A) receptors, especially of short-acting benzodiazepines. Short-acting benzodiazepines are established to rapidly lose their hypnotic effect upon repeated administration. To investigate the tolerance potential of allopregnanolone, we assessed sleep-wake behavior in rats during subchronic treatment (once daily for five days) with placebo or 15 mg/kg allopregnanolone (n = 8 each). The sleep patterns of the placebo and allopregnanolone group did not differ significantly before and after treatment. Throughout the entire treatment period the allopregnanolone group exhibited shorter non-rapid eye movement sleep (non-REMS) latencies, prolonged REMS latencies, longer non-REMS episodes, more pre-REMS and less low-frequency, but higher spindle activity in the electroencephalogram (EEG) within non-REMS than the placebo group. The lack of tolerance effects suggests that allopregnanolone may be an efficacious modulator of sleep-wake behavior over longer time periods than most drugs targeting the benzodiazepine binding site of the GABA(A) receptor.