We have investigated the anatomical distribution and postnatal development of D-aspartate and D-serine in the rat brain and periphery using HPLC techniques. D-Serine was confined predominantly to the brain throughout postnatal life. At birth, a substantial quantity of D-serine was observed throughout the brain areas. The cerebral D-serine content increased from birth to postnatal week (PW) 3 and remained constant thereafter, whereas the cerebellar D-serine content peaked at PW1. In contrast, the transient emergence of D-aspartate was found in almost all brain and peripheral organs. A substantial quantity of D-aspartate was also seen in all brain areas at birth, whereas the D-aspartate content in the cerebrum and cerebellum decreased dramatically by PW1 and 7 respectively. Further, the D-aspartate content and the ratio of D-aspartate to total aspartate were highest in the adrenal at PW3 (608 +/- 70 nmol/g, 45.9%) and in the testis at PW14 (221 +/- 7 nmol/g, 57.8%) respectively. Because D-serine potentiates N-methyl-D-aspartate receptor-mediated transmission through the strychnine-insensitive glycine site and because D-serine exhibits an N-methyl-D-aspartate receptor-related distribution and development, D-serine may be a tenable candidate for an intrinsic ligand for the glycine site. In contrast, because the periods of maximal emergence of D-aspartate in the brain and periphery occur during critical periods of morphological and functional maturation of organs, D-aspartate could participate in the regulation of these developmental processes of organs.