['To investigate the embryonic and/or endometrial molecular mechanisms underlying the antiimplantation effect of interleukin-1 receptor antagonist (IL-1ra).', 'Controlled experiment.', 'Animal facilities at Stanford University and laboratories of the Instituto Valenciano de Infertilidad and the University of Sydney.', 'Twelve-week-old B6C3F-1 female mice.', 'Intraperitoneal injections of recombinant human IL-1ra during the periimplantation period.', 'Implantation sites, embryonic morphology, and viability. Polymerase chain reaction and immunohistochemistry for integrins and extracellular matrices and transmission electron microscopy of endometrium in IL-1ra-treated versus control animals.', 'Pregnancy rates in control and IL-1ra-injected animals were 60% and 13%, respectively. At day 8 of pregnancy, flushing of uteri obtained from the treated group resulted in 32 blastocysts. Six pseudopregnant animals received IL-1ra-treated blastocysts (left horn) and control blastocysts (right horn), resulting in one pregnancy, with two embryos and one embryo in the left and right horns, respectively. At day 4 of pregnancy, IL- 1ra down-regulated alpha4 mRNA with use of the polymerase chain reaction. Immunohistochemistry showed a decrease of alpha4, alpha v, and beta3, and transmission electron microscopy revealed inhibition of transformation of the plasma membrane.'] Does interleukin-1 receptor antagonist prevent embryonic implantation by a direct effect on the endometrial epithelium?