The anti-inflammatory cytokines alpha-melanocyte-stimulating hormone (MSH) and interleukin (IL)-10 inhibit acute renal failure (ARF) after ischemia or cisplatin administration; however, these agents have not been tested in a pure nephrotoxic model of ARF. Therefore, we examined the effects of alpha-MSH and IL-10 in HgCl(2)-induced ARF. Mice were injected subcutaneously with HgCl(2) and then given vehicle, alpha-MSH, or IL-10 by intravenous injection. Animals were killed to study serum creatinine, histology, and myeloperoxidase activity. Treatment with either alpha-MSH or IL-10 did not alter the increase in serum creatinine, tubular damage, or leukocyte accumulation at 48 h after HgCl(2) injection. Because alpha-MSH and IL-10 are active in other injury models that involve leukocytes, we studied the time course of tubular damage and leukocyte accumulation to investigate whether leukocytes caused the tubular damage or accumulated in response to the tubular damage. Tubular damage was present in the outer stripe 12 h after HgCl(2) injection. In contrast, the number of leukocytes and renal myleoperoxidase activity were normal at 12 h but were significantly increased at 24 and 48 h after injection. We conclude that neither alpha-MSH nor IL-10 altered the course of HgCl(2)-induced renal injury. Because the tubular damage preceded leukocyte infiltration, the delayed leukocyte accumulation may play a role in the removal of necrotic tissue and/or tissue repair in HgCl(2)-induced ARF.