Apelin, a peptide first isolated from bovine stomach extracts, was discovered as an endogenous ligand for the APJ receptor. APJ has been shown to be a co-receptor for human and simian immunodeficiency virus (HIV and SIV). Apelin specifically inhibited the entry of primary T-tropic and dualtropic HIV-1 isolated from different clones expressing antiviral CD4 and APJ. On the basis of these results, we decided to compare the apelin expression level between normal and AIDS-infected tissues by immunohistochemistry. We found that apelin expression was less intense in AIDS-infected tissues compared to normal tissues, in particular in the pancreas, kidney, adrenal glands and lymphoid organs. These results suggest an involvement of this peptide in immunodeficiency and in the immune response to AIDS.