The roles of norepinephrine (NE) and epinephrine in behavior were investigated by targeted disruption of the dopamine β-hydroxylase (Dbh) gene, thereby eliminating these compounds in vivo. Most heterozygous pups born to Dbh−/− females died within several days of birth and were often found scattered within the bedding. Potential causes including deficits in olfaction and lactation were not apparent. A deficit in maternal behavior was confirmed by the lack of pup retrieval exhibited by Dbh−/− virgin females. Restoration of NE shortly before but not after birth induced females that previously abandoned their litters to act maternally. Our results suggest that NE is responsible for long-lasting changes that promote maternal behavior during both development and parturition in mice.