We investigated the effect of axotomy, deafferentation, and deafferentation plus axotomy on cell survival and cell size in Clarke's nucleus of the cat spinal cord. Hemisection of the adult spinal cord at T9 leads to retrograde cell death of 40% of the neurons in Clarke's nucleus at L3, as well as to a reduction in the mean soma size of the survivors. In contrast, deafferentation of Clarke's nucleus neurons by L1-S2 dorsal rhizotomy produces no cell loss and no shrinkage of the somata. These results indicate that dorsal root afferent input is not required for Clarke's nucleus cell survival. To test whether afferents may be required by the 60% of neurons that survive axotomy, we deafferented Clarke's nucleus prior to axotomy. Surprisingly, removal of primary afferents to Clarke's nucleus neurons prior to axotomy prevented the death of all neurons that would normally have died from axotomy. These results suggest that dorsal root afferent input is not required for Clarke's nucleus neuron survival after axotomy and may in fact be toxic to these axotomized neurons. This afferent toxicity is likely to be mediated through the dorsal root afferent neurotransmitter glutamate.