This review examines possible relationships between anorexia, dietary intake and central nervous system histaminergic activity. The hypothesis being reviewed is that one component of normal or pathophysiological neuroregulation of food intake involves histaminergic activity in the central nervous system, as influenced by concentrations and bioperiodicities of histamine and/or histamine receptors. Changes in concentrations of receptors are gender specific. Low protein quality or quantity diets elevate both central histamine and histamine receptors (H1) in rats while significantly decreasing their food intake. When injected with histaminergic antagonists, rats fed low protein diets increase food intake and have improved efficiency of weight gain. This review supports a dual hypotheses: central histaminergic activity is involved in the regulation of food intake, but food intake patterns (including dietary composition or energy content) can modify central histaminergic activity. This review also suggests that modified histamine and/or H1 receptor concentrations are potential mechanisms for elevated central histaminergic activity in food intake-related pathophysiological states. Thus, dietary interventions (clinically- or self-imposed) which modify food intake or diet composition have the potential of affecting the histaminergic system. Also, drugs with antihistaminergic properties have the potential of affecting food intake/weight gain patterns by interfering with normal neurochemical signals.