The effects of negative energy balance on self-stimulation are a matter of considerable disagreement. This disagreement undoubtedly reflects the inadequacies of the continuous reinforcement self-stimulation procedures used in this type of experimentation. The present experiment uses a new fixed-interval reinforcement shuttle-box procedure which provides indices of reward and stimulation escape that are free from the numerous performance altering effects that confound continuous reinforcement performance. Whereas 24 h of food deprivation had no effect on stimulation initiation or escape rates, 48 h of food deprivation selectively increased initiation rates. The enhancement of reward was seen over virtually the entire anterior-posterior extent of the lateral hypothalamus and occurred irrespective of the occurrence of any stimulus-bound behaviors. Thus negative energy balance appears to selectively increase the excitability of reward-related neurons in the lateral hypothalamus. The self-stimulating rats became clearly hyperphagic, yet their weight gains were not significantly different from those of controls. The self-stimulation must, therefore, have greatly increased energy expenditure. Thus, not only does energy balance affect self-stimulation, but self-stimulation appears to affect energy balance.