Bone specific alkaline phosphatase (B-ALP) is a new marker of bone formation. The effect of perinatal factors on neonatal B-ALP concentrations is unknown. Weight relative to gestation & season of birth are important factors influencing newborn bone metabolism. Previously, we found apparent evidence of decreased bone turnover, ie. low osteocalcin (OC) in small (SGA) vs appropriate for gestation (AGA) infants (J Ped 1993;122:269); & low OC in winter- vs summer-born AGA newborns (JPGEN 1994;19:220). Alkaline phosphatase (ALP) functions as a cell surface enzyme of osteoblast, & has a significant role in skeletal mineralization; calcification is blocked when ALP activity is inhibited. Blood B-ALP & OC concentrations reflect different stages of osteoblastic activity; B-ALP reflects early osteoblastic activity, whereas OC reflects late. We hypothesized that SGA infants will have lower B-ALP than AGA infants, reflecting decreased bone turnover; winter AGA newborns will have lower B-ALP than summer newborns; there would be no differences by sex or race. 195 term AGA (x±SD, 38.5±1.1 wk, 3344±349 g) & 71 term SGA infants(38.4±1.2, 2329±193, p<0.001) were studied prospectively; 82 AGA infants were born in winter (Jan-Mar; 39±1, 3335±380) & 79 in summer (Jul-Sep; 39±1, 3398±388); 98 male, 97 female; 103 white, 92 black. Cord serum B-ALP was measured by enzyme immunoassay(Alkphase-B, Metra Biosystems, Mountain view, CA); intra-& inter-assay%CV, 3.5% & 7.9%, respectively (normal adults 10 to 23 U/L). SGA infants have higher B-ALP than AGA (55.5±13.2 vs 49.9±14.1 U/L, p=0.016). Winter AGA newborns have higher B-ALP than summer newborns (W vs S, 47.4±14.9 vs 41.6±15 U/L, p=0.016). There was inverse relationship between bone mineral content & B-ALP(r=-0.352, p=0.02); & B-ALP & OC (r=-0.208,p=0.012). Serum B-ALP was not different by sex or race. Thus, in newborn infants, B-ALP concentrations were higher in SGA vs AGA; & in winter vs summer births. We speculate that early osteoblastic activity (matrix development & maturation) is increased in SGA & in winter-born AGA newborns: decreased mineral transport across the placenta, in SGA or in winter, may lead to adaptive mechanisms in fetal osteoblastic activity.