During pregnancy and lactation in rodents, STC-1 production by the ovaries is upregulated markedly and released into the circulation. The mammary glands are one target of this systemically delivered hormone. The purpose of this study was to lower serum levels of STC-1 in lactating mice through passive immunization, so as to monitor the effects on mammary gland function and post-natal pup growth. Passive immunization significantly reduced circulating hormone levels and pup growth was significantly compromised (30%), even though control and experimental litters ingested equal amounts of milk. When the mammary glands were analyzed, alveolar area was significantly reduced in antibody-treated mothers. An analysis of milk composition revealed no changes in lactose, protein or electrolytes, but a 40% reduction in triglyceride levels. The latter was due to a significant reduction in mammary gland lipoprotein lipase activity, and led to a build up of triglycerides in the serum. Body fat content was also significantly reduced in pups from antibody-treated mothers, whereas pup fecal fat content was increased. In mothers, passive immunization also caused significant behavioral effects; in particular, increased locomotor and hind leg rearing activities. Collectively, the results suggest that systemically derived STC-1 has important effects on mammary gland development and the transfer of serum-based triglycerides into milk. The locomotor effects suggest that STC-1 also has a role in maternal behavior.