The long-sleep (LS) and short-sleep (SS) lines of mice were derived by selective breeding with respect to ethanol sleep time. We found that in current generations LS mice also have longer sleep times than SS mice to trichloroethanol and paraldehyde. Two subsequent experiments tested our hypothesis that mice that are relatively insensitive to the hypnotic effects of depressant drugs might be relatively activated by low doses of these drugs. Both experiments failed to support the hypothesis. First, although SS mice were more activated than LS mice by subhypnotic doses of paraldehyde, the lines did not differ in the degree of activation produced by low doses of trichloroethanol. Second, among mice from a genetically heterogeneous population (HS), there was no relation between the degree of activation induced by a low dose of ethanol and sensitivity to the hypnotic effects of a higher dose.