Studies are reviewed in which response to acute administration of alcohol was compared between individuals with and without family histories of alcoholism (FH+, FH-). This research represents a search for a psychobiological marker for alcoholism. A methodological critique of the procedures reported in this literature is then presented. Finally, a conceptual model is suggested in which differences in the response to alcohol between FH+ individuals and FH- individuals must be understood in relation to time after drinking alcohol. This Newtonian differentiator model proposes that sons of alcoholics exhibit acute sensitization as blood alcohol level rises and acute tolerance as blood alcohol level falls, compared with sons of nonalcoholics. Therefore, FH+ subjects find alcohol more rewarding because they accentuate the pleasurable, excitatory aspects of initial intoxication and attenuate the feelings of anxiety and depression that predominate as blood alcohol levels drop.