OBJECTIVE To measure angiogenin, a potent inducer of neovascularization and interleukin-6, as an indicator of acute inflammation, in second-trimester amniotic fluid of patients with elevated maternal serum hCG. METHODS In this case-control study, 20 patients with elevated maternal serum hCG (at least 2.0 multiples of median) at triple screen were matched 2:1 with controls on the basis of year of amniocentesis, parity, and race. Inclusion criteria were 1) singleton gestation, 2) no evidence of anomalies, and 3) genetic amniocentesis. Amniotic fluid was immunoassayed for angiogenin and interleukin-6. The immunoassay sensitivity for angiogenin was 0.026 ng/mL, interassay coefficient of variation 4.6%, and intra-assay coefficient of variation 2.9%. For interleukin-6, the immunoassay sensitivity was 2.37 pg/mL, interassay coefficient of variation 2.7%, and intra-assay coefficient of variation 1.9%. Angiogenin and interleukin-6 values were normalized by using natural log transformation for statistical analysis. Statistical analysis included analysis of variance and stepwise regression, with P < .05 significant. RESULTS After correcting (by multivariate regression) for gestational age at sampling and nulliparity, amniotic fluid angiogenin levels were significantly lower in the study subjects than in controls (26%+/-11% lower, P=.004), whereas the interleukin-6 levels did not change significantly (34%+/-40% lower, P=.3). CONCLUSIONS Amniotic fluid angiogenin levels are significantly lower in patients with elevated maternal serum hCG at triple screen, suggesting inadequate angiogenesis, but interleukin-6 values do not differ significantly.