The brainstem and cervical spinal cord were sampled from 45 cases of sudden infant death syndrome (SIDS), from 17 control cases without neurological disease, and from three negative control cases with abnormal growth of the central nervous system (36-98 postconceptional weeks). Morphometric analyses were performed on serial Nissl sections to determine the total volumes of the pons, nucleus pontis, medulla and cervical spinal cord. Normal development was characterized by a linear increase in the volumes of these regions during the first postnatal year. Regression analysis revealed that in SIDS cases the rates of increase in the volumes of the pons and nucleus pontis were significantly greater than in controls (56% and 83%, respectively), while growth rates did not differ significantly for the medulla and cervical spinal cord. By direct comparison, there was a significant increase in the mean volumes of the pons (33%), nucleus pontis (38%) and medulla (19%) in SIDS cases when compared to controls. No evidence of excessive edema or gliosis was noted in the brainstem by light and electron microscopy to account for the increased volumes. Subtle morphological abnormalities in brainstem neurons from SIDS cases, including an increased size of Nissl bodies in the cytoplasm of large motor neurons and the presence of paranucleolar coiled bodies, were consistent with an increased synthesis and transport of ribosomal RNA, an increased synthesis of cellular proteins and neuronal hypertrophy.