The objective was to determine the relationship between plasma alkaline phosphatase (AP) activity and birthweight (BWT) and preterm delivery (PTD). Five hundred eighty African-American women had plasma AP activities measured at various gestational ages (GA) with the results compared to a number of pregnancy outcomes. Plasma AP activity rose linearly during pregnancy from a mean of 39 U/L at 19 weeks to 130 U/L at delivery. In individual women, AP activities were consistently high or low as confirmed by correlation coefficients in adjacent time periods ranging from 0.63 to 0.87. AP at 19 weeks was not significantly associated with any outcome measure. However, at 26 weeks, AP in the highest quartile was associated with a 15.0% incidence of PTD < 37 weeks compared to 6.8% in the lower three quartiles (P = .004). For PTD < or = 32 weeks, the difference of PTD was 6.8 vs. 1.6% (P < .003). When women in the highest quartile of increase in AP from 19 to 26 weeks were compared to those in the lower quartiles, the rate of PTD < 37 weeks was 15.2 vs. 6.4% (P = .002), and the rate of PTD < or = 32 weeks was 6.1 vs. 1.7%, (P = .01). The mean BWT for the highest vs. the lower three quartiles in rate of increase was 3,058 vs. 3,288 g (P = .0005) and the mean GA was 38.1 vs. 39.2 weeks (P = .0001). Regression analyses adjusting for multiple confounders confirmed the association between high AP at 26 weeks and PTD < 37 weeks [OR (95% C.I.), 2.4 (1.2-4.8)] and PTD < or = 32 weeks [OR (95% C.I.), 3.7 (1.2-11.7)]. Similar results were found among women with a large increase in AP between 19 and 26 weeks. From these results we conclude that high or increasing AP activity at 26 weeks, but not 19 weeks, was significantly associated with subsequent PTD and a lower BWT.