The anti-inflammatory cytokines α-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 α-MSH and IL-10 in HgCl₂-induced ARF. Mice were injected subcutaneously with HgCl₂ and then given vehicle, α-MSH, or IL-10 by intravenous injection. Animals were killed to study serum creatinine, histology, and myeloperoxidase activity. Treatment with either α-MSH or IL-10 did not alter the increase in serum creatinine, tubular damage, or leukocyte accumulation at 48 h after HgCl₂ injection. Because α-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 HgCl₂ 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 α-MSH nor IL-10 altered the course of HgCl₂-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 HgCl₂-induced ARF.