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One hundred twenty-six consecutive cases of sudden and unexpected death in children between the ages of 10 days and 2 years were studied. Anatomic and microbiologic studies were carried out and an investigation was made at the home in each case. Both sexes were equally vulnerable. Eighty-five per cent of the children were less than 6 months old. The peak incidence was at 2 months. Ninety-nine children were found dead and 27 were observed to die. The same variety and severity of anatomic lesions were found in both categories. Sixteen children in the same age range who died rapidly following known lethal voilence were studied as a control group. Of the nontraumatic sudden death ("unexplained") series 106 (84 per cent) revealed microscopic inflammatory changes in 1 or more sites of the respiratory tract, and histologic evidence of inflammatory disease in other organs was seen in many cases. Acute hemorrhagic pulmonary edema was a common anatomic finding (82 per cent). It was usually accompanied by visceral and cerebral congestion and hemorrhages. Special investigative procedures including staining of the liver for glycogen, determination of the glucose level of the cerebrospinal fluid and study of the adrenals for sudanophilia and birefringence indicated that these factors are without significance in sudden death in early life. A variety of congenital and acquired abnormalities, the presence of which had been unsuspected, was demonstrated at necropsy. Eleven per cent of the 126 cases showed no anatomic abnormalities other than the circulatory phenomena. No single bacterial organism or group of organisms was isolated with any degree of consistency from any site. All attempts to isolate viruses were negative. Ante-mortem symptomatology, circumstances of death, history of contact with infectious disease, and past history of repeated respiratory infection were without prognostic significance and were not pathognomic as to the cause of death. Eighty children had histories of mild illness for 48 hours or less prior to death. Fifty-three children had received some form of treatment during this interval. Sixty-nine children had histories of contact with infectious diseases. Forty-one children had past histories of repeated respiratory infections. The cases came from every social level. Sixty-five per cent had received good care while 35 per cent had received poor care. Many of the control cases showed inflamatory disease in the respiratory tract similar to that seen in the natural death group as well as anatomic evidence of lethal trauma. The inflammatory lesions are thus not incompatible with life. Several hypotheses are offered in an effort to link microscopic inflammatory respiratory tract changes with hemorrhagic pulmonary edema and sudden death. Anatomic and anamnestic evidence exclude mechanical suffocation by bedding. No statement as to the cause of death of an infant who has died suddenly and unexpectedly should be made without complete gross and microscopic studies and thorough investigation of the scene and circumstances of death.