Previous pathological reports have indicated that swollen and vacuolated motoneuron cell bodies are the most predominant feature characterising Wobbler mouse motoneuron disease, but there has been little supportive evidence using area measurements. The present study focuses on the possible role of changes in neuronal nuclear and perikaryal volumes in the cervical spinal cord ventral horn, using new and traditional stereological probes which provide unbiased estimates of volume. Semithin sections from the ventral horn of Wobbler mice and age and sex-matched phenotypically normal littermates were examined at 2 ages (young and old). The young Wobbler group had significantly larger volume weighted mean perikaryal volumes compared with age-matched controls, reflecting the presence of large swollen cells characteristic of this group; this situation was reversed in the control group. Number-weighted perikaryal volume estimates in the old Wobbler group were smaller than in age-matched controls. The variation in perikaryal volume was greatest in the young Wobbler group in which the coefficient of variation was 127%. The mean number weighted and volume weighted mean nuclear volumes were significantly smaller in the old Wobbler group compared with age-matched controls and young Wobbler groups. The application of new stereological probes has enabled us to document more precisely these changes in neuronal structure in the Wobbler mutant mouse.