Lactating females that fiercely protect offspring exhibit decreased fear and anxiety. The authors tested whether decreased corticotropin-releasing factor (CRF), an activator of fear and anxiety, plays a functional role in maternal aggression. Intracerebroventricular (icv) injections of CRF (1.0 and 0.2 microg, but not 0.02 microg) significantly inhibited maternal aggression but not other maternal behaviors. The CRF antagonist D-Phe-CRF(12-41) had no effect. Maternal aggression and icv CRF (0.2 microg) induced Fos in 11 of the same regions, including the lateral and medial septum, the bed nucleus of the stria terminalis, the medial and central amygdala, the periaqueductal gray, the dorsal raphe, and the locus coeruleus. These findings suggest that decreased CRF is necessary for maternal aggression and may act by altering brain activity in response to an intruder.