Ribonucleotides in human milk have been claimed to have several effects in recipient infants. It is, however, not known whether the nucleotides found in human milk result from degradation of nucleic acids or are actively secreted as a response to a nutritional demand of the infant. Furthermore, little is known of the newborn infant's endogenous capacity to digest nucleic acids to absorbable products. We therefore analyzed human milk, during established lactation, with respect to the concentration of nucleic acid and ribonucleotide metabolites. Expressed as nucleotide equivalents, 68 +/- 55 mumol/L were present as nucleic acid, 84 +/- 25 mumol/L as nucleotides, and 10 +/- 2 mumol/L as nucleosides. The nucleotide/nucleoside profile showed a substantial predominance for pyrimidines and uric acid. This specific profile could, at least to some extent, result from limited catalysis during storage of the milk in the breast, because enzymes capable of degrading nucleotides were found in the milk. To evaluate the endogenous capability of newborn infants to metabolize RNA and nucleotides, fetal small intestine was analyzed for relevant digestive enzymes. Such intestine, from a fetus of 22-wk gestation, digested RNA to cytidine, uridine, and uric acid in vitro. Furthermore, a fetal small intestinal homogenate generated a net increase in pyrimidines and purines when incubated with human milk, whereas when incubated with infant formula, devoid of nucleic acids, it did not.