Interactions between serotonin and corticotropin-releasing factor (CRF) have been demonstrated by various studies in different parts of the brain. Both are activated by stressful stimuli. Additionally, serotoninergic fibres directly synapse with the parvocellular division of the paraventricular nucleus (PVN) that mainly synthesize CRF. The functional impact of this serotonin-CRF interaction on CRF-induced responses remains unclear. CRF infusion into the brain evokes a specific pattern of behavioural, endocrine and neuronal changes that resemble those following various forms of stress. The aim of the present study was to investigate the effects of serotonin depletion on acute CRF-induced c-fos expression, corticosterone levels and behavioural responses. Lateral ventricular (i.c.v.) infusion of CRF (250 pmol) resulted in a significant increase in grooming, corticosterone and c-fos mRNA in the PVN. Adequate and specific depletion of serotonin using 5,7-DHT did not alter these CRF-induced changes. These data suggest that acute responses induced by i.c.v. CRF are independent of basal levels of serotonin.