The morphology of growth cones of regenerating optic nerve axons was examined by light and electron microscopy in adult frogs (Rana pipiens), using a horseradish peroxidase (HRP) fiber-filling method, during early and later phases of regeneration. Optic nerve regeneration was initiated unilaterally by crushing the optic nerve in mid-orbit. Fiber filling was accomplished by severing the affected nerve closer to the eye 24-48 hrs. prior to sacrifice and applying HRP to the central stump. Regenerating axons and their growth cones were observed in the optic nerves, chiasma, tract, pretectal neuropil, and optic tectum. Growth cones of normal-appearing axons varied in shape and size. Flattened, foliate growth cones similar to those commonly described in vitro were observed in the pretectal neuropil and optic tectum. Other growth cones having vermiform, lanceolate, spatulate, and bulbous forms were observed throughout the optic pathway at all stages examined, although the longer (up to 70 micrograms) wormlike structures appeared only in the optic tract during the early period of outgrowth. Nearly complete serial-section reconstructions were obtained for two growth cones in the contralateral optic tectum at 8 wks. regeneration time. One was thinly flattened (to 30-50 nm in places) and extended broadly (8 micrograms in diameter) in contact with a neuronal perikaryon. The other formed a hood over the blind end of a severed, nonregenerating myelinated axon, which was normal-appearing except at its end within the confines of the growth cone. Morphological variation among the growth cones is discussed in relation to other descriptive in vivo studies and views concerning growth cone motility.