OBJECTIVE Low birth weight remains the leading cause of perinatal morbidity and mortality, but mechanisms mediating impaired fetal growth are poorly understood. To further define the role of abnormal immune activation and suppression in mediating impaired fetal growth, we measured levels of interleukin-10, a potent immunosuppressive cytokine not previously identified in association with pregnancy, in amniotic fluid samples obtained at genetic amniocentesis. METHODS In a case-control study with an enzyme-linked immunoassay we compared amniotic fluid levels of interleukin-10 in midtrimester samples obtained from appropriate-for-gestational age (n = 42) and small-for-gestational-age (n = 24) pregnancies. RESULTS Interleukin-10 levels in small-for-gestational-age samples were elevated (median 78 pg/ml) compared with levels in control samples (median < 40 pg/ml), p = 0.02. In small-for-gestational-age pregnancies elevated levels were associated with nulliparity, p = 0.003. CONCLUSIONS Our data support the role of abnormal immune activation, as opposed to inadequate immune suppression, in mediating impaired fetal growth.