During development, spinal cord cells of the frog Xenopus laeuis undergo a reduction in size. This phenomenon occurs during neural tube formation and continues at least until the start of metamorphosis. The number and shape of spinal cord cells also changes, but not always in synchrony with the reduction in cell size. The concomitant change in size and number of spinal cord cells during embryogenesis suggests that a cleavage type of reductive division contributes to the decrease in cell size. Blocking cell division with a combination of hydroxyurea and aphidicolin (HUA) stops the decrease in cell size during embryonic development without affecting the differentiation of a specific class of catecholaminergic neurons. HUA treatment during larval stages does not block the decrease in catecholaminergic neuron size. Thus, both mitotic and postmitotic cells decrease in size during spinal cord development. The two mechanisms are prevalent at different developmental stages with reductive division and cellular atrophy common during embryonic and larval phases, respectively. Like other regressive changes such as cell death and synapse elimination, decreases in cell size affect spinal cord morphogenesis and presumably the function of developing spinal cord cells.