The results of numerous studies have provided compelling evidence that CRF plays an important function in the amygdala. Stimulation of the amygdala produces physiological changes similar those observed after central injections of CRF. Central injections of CRF activate neurons in the amygdala as measured by increases in c-fos protein expression. Destruction of cells or injections of CRF antagonist in the amygdala can attenuate some of the central effects of CRF. The amygdala is the origin of major CRF-containing pathways in the brain. Amygdaloid CRF neurons project to widespread regions of the basal forebrain and brain stem. These amygdaloid pathways mainly arise from the central amygdaloid nucleus where there are a large number of CRF immunoreactive neuronal perikarya. Glucocorticoid and CRF-binding protein are located in cells of the central amygdaloid nucleus. CRF neurons in the central nucleus send their axons to the bed nucleus of the stria terminalis, lateral hypothalamus, midbrain central gray, raphe nuclei, parabrachial region, and the nucleus of the solitary tract. Tract tracing studies have suggested that amygdaloid CRF neurons also innervate CRF neurons in some of these regions and, furthermore, that CRF neurons in some of these areas project back to the CRF neurons in the amygdala. Thus, the amygdala is part of a network of brain nuclei interconnected by CRF pathways. In addition, amygdaloid CRF neurons may project directly to dopaminergic, noradrenergic, and serotonergic neurons, which have widespread projections throughout the neuroaxis.(ABSTRACT TRUNCATED AT 250 WORDS)