C-type natriuretic peptide (CNP), a paracrine growth factor promoting vasodilation and angiogenesis, is upregulated in human and ovine pregnancy in response to vascular stress or nutrient restriction (NR) in late gestation. Postulating that maternal plasma CNP products are increased by modest NR (50% of metabolisable energy requirement) early in pregnancy, and further enhanced by litter size, we studied serial changes of maternal plasma CNP in pregnant ewes receiving a normal (NC, n=12) or restricted (NR, n=13) diet from Day 30 to Day 93 or 94 of gestation. Liveweight of NR ewes was 10kg less than that of NC ewes at slaughter. Plasma CNP products increased progressively after Day 40 and were higher in NR (P<0.05) ewes after Day 60; they were also enhanced by litter size (P<0.01) and were positively associated with increased placental efficiency. In contrast, whereas fetal and placental weight were reduced by NR, fetal plasma CNP products (Day 93/94) were not affected. We conclude that increases in CNP during rapid placental growth are further enhanced by both increasing nutrient demands and by reduced supply, presumably as part of an adaptive response benefitting placental-fetal exchange.