Selenium levels were low in four children receiving long-term total parenteral nutrition (TPN) who developed erythrocyte macrocytosis (3/4), loss of pigmentation of hair and skin (2/4), elevated transaminase and creatine kinase activities (2/4), and profound muscle weakness (1/4). Initial mean selenium levels in serum and hair were 38 +/- 11 (SEM) ng/mL and 0.34 +/- 0.13 micrograms/g, respectively. Mean serum vitamin B12, folate, and vitamin E levels were normal. Intravenous supplementation with selenium was begun daily at 2 micrograms/kg/day. After 3 to 6 months, serum selenium levels rose almost threefold to 81 +/- 22 ng/mL. During this same time, erythrocyte mean corpuscular volume fell from 115 +/- 8 fL to 88 +/- 7 fL in the three children with macrocytosis. After 6 to 12 months of supplementation, hair selenium content had increased threefold to 1.02 +/- 0.19 micrograms/g. The two children with decreased pigmentation became darker skinned and their hair color changed from blonde to dark brown; a third child's hair, which had been blonde, also became darker. Transaminase and creatine kinase activities returned to near normal in those affected and, in the one child with severe myopathy, muscle weakness improved. Erythrocyte macrocytosis and loss of skin and hair pigmentation are previously undescribed manifestations of selenium deficiency. We recommend routine supplementation of TPN solution with selenium to avoid the clinical and biochemical syndrome of selenium deficiency in patients receiving long-term TPN.