This paper reviews some of the research on genetic bases of individual differences in ethanol tolerance of mice conducted at the Institute for Behavioral Genetics and at its predecessor laboratory at the University of California, Berkeley. Tolerance is, of course, a complex concept. Theoretical distinctions are made between tachyphylaxis and more slowly acquired tolerance and between dispositional and tissue tolerance. Pragmatically, a variety of measures (such as locomotor activity, sleep time, hypothermia) can be used to define these processes, and the different indices may yield quite different results even when they presumably indicate the same process. It is clear that an understanding of genetic influence in "ethanol tolerance" will require wide sampling of this complex domain. The work described here represents only a beginning, but it may illustrate the general approaches that are available for addressing the issue.