In the frog Rana esculenta the left dorsal habenula includes a lateral and a medial component, whereas the right dorsal habenula is only represented by one nucleus. The efferents of the habenular nuclei to the interpeduncular nucleus were herein investigated with the retrograde horseradish peroxidase tracing. Injections of cobaltic-lysine complex in the interpeduncular nucleus were also performed. Intensely labeled fibers of the fasciculus retroflexus on the right and left sides of the brain were found to reach the interpeduncular nucleus from the habenular nuclei running prevalently in two routes--one through the medial, and the other through the lateral region of the diencephalon. On the right side, these fibers originated from the entire dorsal habenula. On the left side, the fibers of the medial route derived from the medial habenular subnucleus, while those of the lateral route derived from the lateral habenular subnucleus. In the dorsal habenulae of both sides, a large number of neurons displayed a Golgi-like labeling, while few such cells were detected in the ventral habenulae. Labeled neurons in the right dorsal habenula resembled those labeled in the lateral subnucleus of the left dorsal habenula, while larger and ramified neurons were detected in the left medial subnucleus. The present findings provide the first description of the pathway originating from the medial and the lateral subnucleus of the left dorsal habenula in the frog and point out that projection neurons of the medial habenular subnucleus are morphologically different from those of the other habenular nuclei. The present data indicate that in the frog the habenular asymmetry could underlie distinct functional correlates of the left and right habenulae.