Previous reports have demonstrated mercury accumulation and toxicity in oral tissues following exposure to mercury vapor from dental amalgam restorations. In the present study, inflammatory responses to subcutaneously administered mercury were assessed histopathologically and immunocytochemically in a rat model system. A panel of six well-characterized monoclonal antibodies specific for monocytes, macrophage subsets, T and B lymphocytes, and major histocompatibility complex (MHC) class II (la) determinants was used to quantitate alterations in mononuclear cell subsets in situ at time intervals from 2 d to 8 wk. The results revealed acute inflammatory cell infiltration at 2 and 3 d, followed by chronic inflammation that persisted after 8 wk. The numbers of monocytes, resident macrophage subsets, and mononuclear cells expressing la antigen were significantly different from control tissues at 1-2 wk. The numbers of resident macrophages remained significantly higher even after 8 wk. These data showed that in situ mercury accumulation can lead to altered expression of MHC class II determinants with persistent chronic inflammation and shifts in mononuclear cell subpopulations.