Pellagra in the human is characterized by the clinical" three D's," namely, dermatitis, diarrhea, and dementia. Newborn mice that received a single intraperitoneal injection of 6-aminonicotinamide (6-AN)(50 mg/kg body weight), an antagonist of niacin, consistently developed lesions in the skin, intestinal tract, and central nervous system. Anterior horn cells in the spinal cord as well as motor neurons in the brain showed the ultrastructural features of neuronal chromatolysis, while glial and ependymal cells showed postinjection (PI) edematous changes on Day 5. In the skin, correlating with clinical delay of hair growth, the first discernible microscopic abnormality was vacuolar change in the hair follicles on PI Day 3. By PI Day 5, hyperkeratosis and irregular acanthosis were noted. Edematous swelling of the enteric glial cells was observed in the myenteric plexus of the descending colon on PI Day 5. Although the pathologic features of these 6-AN-treated mice may not be exactly identical to those of human pellagra, possible contributory mechanisms in the development of pellagra lesions may be elucidated by this experimental model.