The effects on spontaneous behaviour after 7 and 14 days of continuous unilateral infusion of brain-derived neurotrophic factor (BDNF, 12 μg/day) and neurotrophin-3 (NT-3, 12 μg/day) into the rat substantia nigra were investigated during the day and night. Animals subjected to these treatments were compared to untreated controls and vehicle-infused controls that were weight-matched for the decreases in body weight produced by BDNF and NT-3. BDNF increased feeding and food retrieval, indicating that BDNF did not decrease appetite. BDNF but not NT-3 markedly decreased drinking, suggesting that weight loss in BDNF-treated rats may be secondary to hypodypsia, whereas in NT-3-treated rats weight loss was more likely a direct consequence of decreased feeding. Exploratory behaviours, limb flicks and contralateral postural bias were increased by BDNF. The behavioural profile of BDNF-treated rats is consistent with an increase in dopaminergic activity. In addition, BDNF increased backwards walking, a behaviour that requires the activation of both dopamine and serotonin systems. In contrast, NT-3 selectively increased behaviours that are mediated primarily by serotonin, such as wet-dog shakes. NT-3 increased limb flicks and mouth movements, but had a smaller effect than BDNF on exploratory behaviour. Vehicle infusions produced behavioural effects consistent with cannula- or infusioninduced damage to the nigrostriatal dopamine system, and some of these effects were reversed by BDNF. Most of the behavioural effects of the neurotrophins are consistent with the view that BDNF increases activity of both dopaminergic and serotonergic systems within the nigrostriatal system, and that NT-3 increases serotonin activity. Effects of BDNF and NT-3 on grooming behaviours, possibly indicative of actions on nigral neuropeptides, provide further evidence of consistencies between reported neurochemical and behavioural effects of neurotrophins.