The residual effects of dihydroergotoxine mesylate (DHET: active substance of Hydergine®), ethanol, and DHET + ethanol were investigated in aging male mice. Prolonged alcohol or DHET consumption was found to prolong hexobarbital sleeping time and increase oxygen consumption. Administration of alcohol combined with DHET inhibited the ability of each drug to prolong hexobarbital sleeping time and increase oxygen consumption. There were no significant differences between groups in forebrain synaptosomal (Na+-K+) adenosine- triphosphatase and acetylcholinesterase activity or cerebellar protein, DNA and RNA content. The relative proportion of phospholipid to protein in isolated myelin of the medulla was significantly reduced, whereas the sphingomyelin content of total phospholipid was highest in alcohol-treated mice. Concomitant treatment of mice with alcohol combined with DHET prevented the physiological and neurochemical changes caused by alcohol and, in some cases, DHET, administered alone