It is well-established that the secretion of the opioid neuropeptide beta-endorphin is perturbed by the administration of various drugs of abuse. Several investigators have speculated that variations in beta-endorphin secretory regulation may precede the development of a substance use disorder, and thus be a component of the liability for substance abuse. In order to test this hypothesis, we examined fasting, morning plasma concentrations of beta-endorphin and two catecholamine metabolites in prepubertal boys naive to drugs of abuse and at elevated familial risk for a substance use disorder (SA+), and in controls (SA-). Specifically, the dopaminergic metabolite homovanillic acid (pHVA), and the noradrenergic metabolite, 3-methoxy-4-hydroxy-phenylglycol (pMHPG) were measured. Between-group differences were not found for beta-endorphin, pHVA, or pMHPG. Similarly, such differences did not differentiate sons of fathers with Antisocial Personality Disorder and controls. However, regression analysis revealed that although both pHVA and pMHPG predicted beta-endorphin concentrations to similar degrees, the directions of influence were the opposite. pHVA was found to be positively associated with beta-endorphin while pMHPG was found to be negatively associated with beta-endorphin. No between-group differences in these relationships were found. The results suggest an opponent process in catecholaminergic regulation of beta-endorphin in humans, and are consistent with observations in the central nervous system of animal models.