Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are neurosteroids that have been shown to interact with the GABA system. The present study examined the effects of these compounds in mice on motor activity and behavior in the elevated plus maze. Doses of 0.5 mg/kg and above of DHEA reduced motor activity. This effect was blocked by diazepam, RO15-1788, pentylenetetrazole (PTZ), and ethanol. Both DHEA and DHEAS showed anxiolytic activity in the plus maze test, with DHEA being effective over a very wide range of doses (5 micrograms/kg to 1.0 mg/kg). Both RO15-1788 and PTZ blocked the anxiolytic effect of DHEA, there was no interaction with diazepam, and ethanol enhanced the anxiolytic effect of DHEA. At 1.0 mg/kg, DHEAS blocked the anxiolytic effect of ethanol. These results support the hypothesis that neurosteroids could be involved in the termination of a stress response.