Administration of fenfluramine to rats decreased 1-h food intake and locomotor activity. Short-term (2-6 days) but not long-term (21-25 days) lithium treatment potentiated fenfluramine-induced suppression of food intake. However, neither short-term nor long-term lithium treatment had any significant effect on fenfluramine-induced suppression of locomotor activity. These findings demonstrate a differential effect of lithium treatment on fenfluramine-induced suppression of food intake and locomotor activity. Furthermore, these findings are consistent with results from several other animal and clinical studies demonstrating a differential effect of lithium treatment on two different serotonin-mediated functions.