HLA class II antigen expression and IL-1 production by mononuclear phagocytes are important for antigen-stimulated T-cell activation. We examined these surface antigens and a monocyte marker antigen on fresh cord and adult blood monocytes, macrophages (M phi) derived from monocytes in vitro, human placental (fetal) M phi, from adult women. By FACS analysis, we found less DR on cord blood monocytes (80 +/- 7) than on adult monocytes (96 +/- 1) with greater heterogeneity in density of DR due to a weakly staining subpopulation of cord monocytes. There were markedly fewer DR and DQ positive placental M phi, 62 +/- 11% and 19 +/- 3%, compared to adult peritoneal M phi, 91 +/- 11% and 87 +/- 13%. DQ was more intense on peritoneal M phi than on any other cell type. Fresh cord monocytes secreted equal or greater amounts of interleukin-1 (IL-1) in response to lipopolysaccharide (LPS) or Group B streptococci than adult monocytes, although results with individual preparations varied. By Northern blot analysis, LPS-stimulated cord blood and adult monocytes contained similar amounts of IL-1 alpha, IL-1 beta and DR alpha mRNA. Each placental M phi preparation secreted IL-1 (200 +/- 85 U/ml to LPS). Peritoneal M phi preparations from women in the pre-luteal phase did not release detectable IL-1, whereas those from women in the post-luteal phase released as much as monocytes. Cultured monocytes failed to secrete IL-1 and expressed less DQ than fresh monocytes. Exposure to IFN gamma augmented IL-1 release by adult and cord cells and DQ expression on cord cells. These data indicate that class II antigen expression and IL-1 secretion by mononuclear phagocytes are only in part co-ordinately modulated. The differences between placental (fetal) M phi and adult peritoneal M phi may reflect both tissue-specific differences and generally diminished class II antigen expression on fetal and neonatal mononuclear phagocytes.