Objective: To compare cytokine expression profiles of decidua basalis (containing trophoblast cells) and decidua parietalis (without trophoblast cells) for determination of microenvironments in human first trimester decidua. Design: Retrospective study. Setting: School of Medicine, RWTH University of Aachen, Aachen Germany, and Bourgognekliniek Maastricht, Maastricht, The Netherlands. Patient(s): Forty-six women who had undergone elective first-trimester termination of viable pregnancy at 5 to 12 weeks. Main Outcome Measure(s): Quantitative cytokine protein analysis in decidual tissues by enzyme-linked immunosorbent assay, qualitative cytokine messenger (m)RNA analysis in isolated decidual cell samples, and comparative mRNA and protein analysis in tissues of decidua basalis compared with decidua parietalis. Result(s): Interleukin-2, interferon-gamma (Th-1). interleukin-4 (Th-2), and interleukin-1beta proteins are expressed in the human first-trimester decidua. Interleukin-2, interferon-gamma, and interleukin-4 mRNA mainly derive from the decidual tissue leukocytes. Interleukin-1beta mRNA is expressed by all decidual cell types. Interferon-gamma mRNA and protein is detected predominantly in the decidua basalis, which contains trophoblast cells. Conclusion(s): Microenvironments are established topographically by different expression of cytolkines in decidua basalis and decidua parietalis. These locally specific patterns are indicative of fetomaternal cross-talk. Higher interferon-gamma concentrations in decidua basalis may influence leukocyte differentiation (e.g., macrophage activation) and trophoblast invasion (e.g., by induction of expression of major histocompatibility complex). (C) 2003 by American Society for Reproductive Medicine.