It is proposed that the primary cell involved in amyotrophic lateral sclerosis (ALS) is the corticomotoneuron. The spinal motoneuron becomes affected as a result of antegrade effects. This hypothesis does not negate most of the presently popular theories regarding the pathogenesis of ALS, but directs focus to one cell type--the corticomotoneuron. It takes cognizance of the complex, monosynaptic, corticomotoneuronal-spinomotoneuronal connections that have evolved in primates, and especially in man. It might explain the lack of any natural or thus far induced animal model which closely mimics the human disease. Threshold measurements to transcotical magnetic stimulation might be used to test the hypothesis. Replication of ALS in an animal is only likely to succeed in a nonhuman primate.