Zaleplon, a new pyrazolopyrimidine hypnotic, possesses an unusually short elimination half-life (ca 1 h). This study was conducted to determine whether middle-of-the-night administration of zaleplon aects memory or driving performance the following morning. Twenty-eight healthy volunteers participated in a double-blind, 7-way, crossover study. They ingested capsules twice on each treatment night; once before initiating sleep and again after being brie¯y awakened 5 h later. Treatments were: placebo at both times, zaleplon 10 or 20 mg, or zopiclone 7 . 5 mg followed by placebo, or the same in reverse order. Subjects arose 3 h after the second dose. One hour later, sleep quality and mood were assessed by questionnaires and balance and memory in a test battery. A standardized actual driving test was undertaken between 5 and 6 h after the second dose. All drugs similarly improved sleep quality, but only zopiclone hindered awakening. Evening zaleplon doses were without signi®cant eects. Late-night zaleplon had minor eects in one memory test. Evening zopiclone shared these eects and also signi®cantly impaired driving performance. Late-night zopiclone's eects were signi®cant in every test. Its eects on driving were severe. The results suggest that zaleplon 10 mg certainly, and 20 mg probably, can be taken at bedtime or later in the night, up to 5 h before driving with little risk of serious impairment. #