The human genome contains many different types of endogenous proviruses and retrovirus-like elements. An unusual element of this kind has been isolated from human DNA on the basis of its relatedness to the integrase-coding domain of the pol gene of feline leukaemia virus (FeLV). The element, termed Hs5, is related to FeLV only over a short region of 81 nucleotides predicted to encode the carboxyl terminus of the FeLV integrase protein, p46pol. The region of relatedness between Hs5 and FeLV identifies a short conserved amino acid stretch which is shared among distantly related retroviruses. The conservation of this sequence, its position, and predicted secondary structure suggest that it may represent a conserved substrate binding site or active site of the integrase enzyme. Nucleotide sequence analysis of Hs5 reveals that it is not an intact retrovirus, but contains only the 3' terminus of pol and a defective env gene without apparent long terminal repeat; Hs5 is unusual among human endogenous retrovirus-like elements in this respect.