Pineal glands from 16 infants ranging from 38 weeks gestation to 3 years of age were fixed in buffered formalin; Paraffin sections were stained for neuron-specific enolase, glial fibrillary acidic protein, and S-100 protein (S-100) using the peroxidase-antiperoxidase method and hematoxylin and eosin, Masson-Fontana, and Bodian stains. The pineal glands of neonates consisted of cords of closely packed, dark, nucleated cells (type I) with intervening loosely arranged, large, clear cells (type II). The type I cells were frequently pigmented and occasionally exhibited rosette formation. They were positive for S-100 and negative for neuron-specific enolase. The type II cells were strongly positive for neuron-specific enolase and negative for melanin and S-100. The type I cells were the predominant cell type at birth; however, the number of type II cells gradually increased with age, and by the age of 1 year, only scattered S-100 positive cells, consistent with sustentacular cells, were found. The findings indicated that the human pineal glands undergo a remarkable morphologic and functional evolution as an endocrine organ in the postnatal life.