A study of the efferent projections of the entorhinal area in the guinea pig, by using anterograde (autoradiographic tracing of tritiated amino acids) and retrograde (fluorochrome tracing) methods, revealed the following projections: (1) to nonhippocampal cortices: retrosplenial cortex (area 29), cingulate cortex (areas 23, 24), prelimbic cortex (area 32), infralimbic cortex (area 25), perirhinal cortex (areas 35, 36), prepyriform cortex (area 51B), and insular cortex (areas 13-16). All received direct projection; (2) to subcortical targets: distinct terminations were observed in the lateral thalamic nucleus, the striatum, and the accumbens nucleus. In retrograde experiments, the cells giving rise to the projections to the hippocampus were found to lie in layers II and III, those projecting to the nonhippocampal cortical regions to originate in layer IV, and those projecting to the striatum and the accumbens to lie in layers V and VI. Many of the efferent projections to the cerebral cortical regions are associated with reciprocal projections from these regions to the superficial layers (I-III) of the entorhinal cortex. The entorhinal efferent projections generally terminate ipsilaterally. A weak termination is, however, present at the contralateral side. The efferent projections of the entorhinal area represent a route for important caudally directed, nonfornical hippocampal output.