['Placental growth hormone (PGH) is synthesised by the placenta, and its function is modulated by growth hormone binding protein (GHBP). The potential of PGH and GHBP as maternal serum screening markers for Down syndrome (DS) was examined.', 'Maternal serum concentrations of PGH and GHBP were determined by ELISA in 74 DS and 261 control pregnancies in gestational week 8(+0) to 13(+4). Log(10) MoM distributions of the markers were established. The performance of DS screening was estimated by Monte Carlo simulation.', 'PGH log(10) MoM (SD) was decreased (p < 0.001) to -0.201 (0.373) and GHBP log(10) MoM to -0.116 (0.265) (p = 0.04), in DS pregnancies (n = 34) in week 8(+0) to 10(+0). In week 10(+1) to 13(+4), neither PGH (p = 0.16) nor GHBP (p = 0.13) was reduced in DS pregnancies. The detection rate (DR) for PGH in screening for DS in week 8(+0) to 10(+0) was 39% for a false positive rate (FPR) of 5%; increasing to 72% in combination with PAPP-A + hCGbeta. PGH + GHBP in combination with PAPP-A + hCGbeta + nuchal translucency (NT) (CUB test) had a DR of 91% compared with 80% for the CUB test.'] Are placental growth hormone and growth hormone binding protein first trimester maternal serum markers of Down syndrome?