The authors analyzed clinicopathologically eight patients with familial amyotrophic lateral sclerosis (F-ALS). We performed the morphometric analysis on size and topographical distribution of the fourth lumbar spinal ventral horn cells, and correlated thus obtained results with the clinical, genetic and neuropathological features of these cases. The patients were consisted of six men and two women with age ranged between 40 and 58 years old. Six cases among them were involved predominantly in the lower-legs with generalized hyporeflexia and no Babinski's sign, which were compatible with the "pseudopolyneuritic" as a clinical form. Two other cases were involved in the upper limbs as the initial symptom and were considered to be "common form". Pathologically, five cases showed multiple system degenerations including the middle root zone of the posterior columns, Clarke's nuclei and posterior spinocerebellar tracts as well as the ventral horns and pyramidal tracts, which were designated as the form of "multiple system degeneration". In addition, three in these five cases were also associated with an extensive neuron loss and marked gliosis in the Onuf's nuclei, subthalamic, red and cerebellar dentate nuclei, suggesting that the involvement in certain F-ALS cases with a form of multiple system degeneration is more extensive in topography than ever believed. In other three cases, the neuronal degenerations were considerably restricted in the somatic motor efferent system, which were consistent with the classical pathology of the sporadic ALS, and were designated as "classical form". Five of seven cases showed a severe motoneuron loss in both the large and small neurons in the ventral horn. These five cases were heterogeneous in the pathological forms "multiple system degeneration" or "classical", but all were "pseudopolyneuritic" in clinical form. Moreover, these extensive motor neuron loss including small ones in the spinal ventral horn was similarly observed in the sporadic pseudopolyneuritic form of ALS cases. In two cases of F-ALS with "common" in clinical form, large motoneurons were fairly well preserved as are in the common form of sporadic ALS cases. Our tentative conclusion is that mode of motoneuron loss in the spinal ventral horn of F-ALS is more correlated to the clinical manifestations rather than the pathological or genetic background.