A review of the neuropathological findings in 50 personal autopsy cases and in the available literature (214 confirmed cases) of infantile spasms demonstrates that this type of early infantile epilepsy occurs in a wide range of cerebral lesions caused by various noxae during different stages of brain development. With regard to morphology and the presumed time of occurrence of the CNS lesions, four groups can be distinguished: (1) embryofetal lesions, including a) cerebral malformations or developmental disorders-agyria-pachygyria (lissencephaly), micrencephaly, micropolygyrias, (hemi)megalencephaly, agenesis of corpus callosum, tuberous sclerosis, heterotopias, cortical microdysplasias, b) metabolic disorders (leukodystrophies, neurolipidoses, spongy dystrophies, Leigh and Alpers diseases, aminoacidopathies); (2) perinatal and postnatal encephalopathies, e.g. polycystic brain, diffuse and lobar sclerosis, ulegyrias, white matter and basal ganglia scars, status marmoratus, hippocampal sclerosis, and cerebellar atrophy; (3) combined embryofetal (developmental) and perinatal or postnatal brain lesions, particularly association of microdysplasias with secondary anoxic or vascular changes; (4) acute vascular and inflammatory brain injuries; (5) cases without definite brain pathology. Evaluation of the available data indicates that embryo-fetal lesions alone or accompanied and/or superimposed by perinatal or postnatal lesions account for about 61% of the cases confirmed by autopsy, in which infantile spasms can be regarded as fetal epilepsies, while a smaller group is featured by perinatal or postnatal lesions occurring in early age, i.e. affecting the immature brain. Similar lesions are observed in cases showing transition of West syndrome to Lennox syndrome. Negative pathology findings in a small number of cases do not necessarily implicate negative pathobiology.(ABSTRACT TRUNCATED AT 250 WORDS)