To ascertain the nature of intracranial self-stimulation (ICSS) interactions between locus coeruleus (LC) and various hypothalamic (HYP) sites, rats were tested with monophasic pulse pair stimulation. When trains of pulse pairs were delivered to a single ICSS site , lower responding occurred at short pulse-pair intervals. However, when the pulses of each pulse pair were split between LC and HYP ICSS sites, response rates at all pulse-pair intervals were elevated well above single-pulse responding, indicating a neurophysiological interaction between these loci. The symmetry of LC and HYP interactions depended upon the HYP electrode placement. Both internal capsule and fields of Forel placements produced asymmetrical LC·HYP interactions in which higher ICSS rates occurred when the LC received the first pulse of each pair than when it received the second pulse of each pair, suggesting a direct, and possibly modulating, influence of the LC upon these HYP placements. Both medial forebrain bundle and perifornical HYP placements produced symmetrical LC·HYP interactions in which similar ICSS rates occurred regardless of site stimulation order, suggesting an indirect, reciprocal influence between the LC and these HYP placements.Theories of intracranial self-stimulation (lCSS) behavior have often questioned whether the many discrete rreuroanatomical loci throughout the brain which subserve the behavior are linked to form an integrated "reward" system or if these loci are independent of one another and only share the common property of ICSS. Among the many means of ascertaining whether ICSS loci form an integrated system is to determine whether stimulation delivered to pairs of ICSS sites will summate and cause increased lCSS responding. Previous studies demonstrated that response rates elicited under simultaneous or nearsimultaneous stimulation of two ICSS sites were significantly greater than the sum of the response rates elicited when each of the sites was stimulated singly, suggesting that a behavioral interaction between the Data collection and analy sis was supported by a CCNY Faculty