Eszopiclone and zolpidem are hypnotics that differentially affect sleep and waking states in adult animals. Therefore, it was of interest to compare their effects on the states of sleep and wakefulness in aged animals. Our objective was to determine the responses to eszopiclone and zolpidem vis-à-vis sleep and waking states in aged guinea pigs and to compare them with the effects of these hypnotics in adult animals. Aged guinea pigs were prepared to monitor sleep and waking states and to perform a frequency analysis of the EEG. Eszopiclone and zolpidem were administered intraperitoneally (1, 3, and 10 mg/kg). Eszopiclone produced a more rapid and greater increase in NREM sleep as well as longer duration episodes of NREM sleep compared with zolpidem. There was also a significant increase in the latency to REM sleep with eszopiclone, but not with zolpidem. EEG power during NREM sleep increased in the delta band and decreased in the theta band following eszopiclone administration, whereas zolpidem had no effect on any of the frequency bands analyzed. In aged as well as adult guinea pigs, eszopiclone is a more effective hypnotic insofar as it produces a shorter latency to NREM sleep, a greater amount of NREM sleep and EEG delta waves. Differences in the effects produced by eszopiclone and zolpidem as a function of the aging process likely reflect the fact that they bind to different subunits of the GABAA receptors, which are differentially reactive to the aging process.