Adenosine 3':5' monophosphate3 (cAMP) and guanosine 3':5' monophosphate (cGMP) are known to participate in the regulation of proliferation and differentiation, the processes intimately associated with maturation of the neonate. We have therefore examined their content in the physiological nutrient of the mammalian neonate, the mother's milk. Widely fluctuating concentrations between 0.1 and 0.7, and between 0.01 and 0.15 nmol/ml, were found for cyclic AMP and cyclic GMP, respectively. Concentrations in human breast milk changed during the 5-to 15-min period of one nursing, during any 24-h period, and also during the total lactation period. Levels of cyclic GMP were generally less fluctuating and were lower during afternoon and evening; they were relatively high at the start of lactation and levelled off during the postpartum period. The ratio of the two cyclic nucleotides also fluctuated widely and was significantly different from the ratio determined on blood plasma collected at the same time. Oxytocin injection had no effect on cyclic AMP content of rat milk. The stomach content of the nucleotide in rat pups remained high for at least 1 h after suckling indicating that cyclic nucleotides remain available for intestinal absorption; whether they have any physiological function in the neonate will have to emerge from further studies.