The search for carriers of a specific biologic risk for alcoholism is ongoing. In addition to seeking “the needle in the haystack,” the need to monitor a broader phenotypic indicator such as Chronobiological interaction is hypothesized. Certain potential mediators of genetic predisposition to alcoholism are subject to periodic rhythmicity in both animal and human investigations. These mediators include prolactin, cortisol, and MOPEG levels along with possible sleep characteristics. Suggestions for future animal and human investigations are outlined using adequate sampling criteria, appropriate rating and recording instruments, and controls predisposed to other psychiatric diagnoses.