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Examination of 50 autopsied cases of human poliomyelitis showed prominent hyperplastic and inflammatory changes in the lymphoid tissues of 41, the most frequent and severe lesions observed save those in the central nervous system. Histologically the germinal centers showed prominent degenerative and regenerative alterations, fluid transudation, giant cell formation, and rare inclusion bodies, all consistent with virus effects. Treatment of mice with x-rays, aminopterin, and adrenocorticotropic hormone increased poliomyelitis infections following intraperitoneal injection of MEF strain virus, potentiated by intracerebrally injected corn starch. This was ascribed to the damage to lymphoid tissues produced by these agents. On the basis of combined morphologic and virus studies, the presence of gastrointestinal, lymphoid, nervous tissue, and nerve cell defense barriers to poliomyelitis virus is suggested. Use of irradiated mice might prove useful in primary isolation of virus from human poliomyelitis.