A panel of monoclonal antibodies against major histocompatibility complex (MHC)- and monocyte/macrophage-associated antigens was used to compare human fetal and postnatal small intestinal macrophage subpopulations. Cryostat sections were stained using an indirect immunoperoxidase technique. Within the human fetal intestine from 12 weeks gestation, the antibody KiM8 identified a widespread population of type I accessory cells, which showed variable expression of HLA-DR. In contrast, the antibody 3.9 identified small clusters of HLA-DR- and HLA-DQ-positive lamina propria macrophages, presumably type II accessory cells. Comparison of fetal with postnatal small intestine revealed mainly quantitative changes, with an absolute increase in 3.9-, KiM8-, KiM6-, 10.1- and UCHMI-positive accessory cells in the postnatal intestine. The proportions of both UCHM1- and KiM6-positive cells relative to the KiM8-positive population was also increased postnatally. The villous population of 3.9- and KiM6-positive interdigitating type II macrophages characteristic of the postnatal lamina propria was largely absent from fetal small intestine. The monoclonal antibody 3.9 further reacted with the cytoplasm of ganglion cells and nerve fibres within the nerve plexuses of fetal and postnatal small intestine. The significance of this cross-reactivity remains unclear.