Background: The morphology of placental detachment sites and the distribution of macrophages were studied in the mouse uterus from day 1 to 3 months post partum. Methods: Uterine morphology was studied using H&E and Mallory's Trichrome staining. Macrophages were identified using the macrophage-restricted antigens F4/80 and FA/11 and the leukocyte beta(2)-integrin CR3 (Mac-1) which is also expressed by neutrophils. Results: The post-partum wound was infiltrated by large numbers of CR3+ F4/80+ FA/11+ macrophages, and CR3+ neutrophils. The wound resolved rapidly and no inflammatory infiltrate or necrotic tissue was seen by day 5 post partum. The area of the detachment wound and the site of the metrial gland of pregnancy resolved into a structure, here called a postpartum nodule, which persisted for at least three months. The post-partum nodule consisted of an outer layer of collagen around a group of nodule-specific cells which could be divided into haemosiderin- and lipid-bearing phenotypes. The lipid-bearing nodule cells were not found after day 20 post partum. Nodule cells were FA/11+ at all times and also expressed leukocyte common antigen. Expression of CR3 and F4/80 was found on nodule cells up to day 9-10 post partum. CR3 expression was found only occasionally after day 10. F4/80 expression was downregulated from day 9-10 to day 20 but was found consistently after day 20. Implantations of second and subsequent pregnancies are known not to occur in the immediate vicinity of post-partum nodules and nodules from successive pregnancies were seen to be separate within the uterus. Conclusions: Since the endometrial area in the immediate vicinity of nodules is inimical to implantation and nodules consist of a group of macrophages, it can be implied that nodule macrophages are exerting some influence on the endometrium in their vicinity. (C) 1994 Wiley-Liss, Inc.