SYNOPSIS. In premetamorphic amphibians, the Mauthner cells (M-cells), a single pair of large neurons, are present in the medulla. M-cells differentiate early, are easily recognized morphologically, and in the axolotl embryo, may be approached experimentally: This system is a unique one for the study of neuronal development. The withdrawal of a neuron from the cell division cycle is an early event in its differentiation. Gastrulae, neurulae and tailbud embryos were each given a single injection of 3H-thymidine. Radioautographs of larvae showed label over M-cell nuclei when injections were made before the end of gastrulation, but not when injections were made at later stages. Thus, the cells that give rise to M-cells cease DNA synthesis during late gastrulation. Unilateral rotations of prospective hindbrain through 180° were performed to see if M-cell axes are specified during neurulation. Rigid axial polarization of the M-cell does not appear to occur in the neurula: The rotated cell regulates and develops normally with respect to its axes. A major source of input to the M-cell is from the ipsilateral vestibular system. To study the interaction of the M-cell with ingrowing axons, unilateral implants of otic vesicles were made anterior to the otic vesicle in host midtailbud embryos. Preliminary data suggests a mechanism for the formation of specific neuronal connections not dependent upon position-time relationships: The ectopic vestibular axons enter the medulla and course caudad to terminate in the region of the ipsilateral M-cell. Whether these axons actually form synapses on the M-cell remains to be established.