It is unclear how neonates respond to noxious stimuli. This study examined the role of neurokinin peptides in 3- and 21-day-old rat pups using the preprotachykinin-A (PPTA) knockout mouse, lacking neurokinin A and substance P. We assessed pain behaviors of these mice before the neurokinin system is putatively active, 3 days after birth, and after this system is active, 21 days after birth. The lack of these peptides failed to alter behavioral responses to nociceptive stimulation in the 3-day-old mice. The 21-day-old mice lacking these peptides were less responsive to 5 microl 2% formalin and to high intensity thermal and mechanical stimuli. Thus, the neurokinins appear not to be an important mechanism in the processing of nociceptive information in the infant.