In this investigation, we examine the interaction between the human immunodeficiency virus type I integrase and oligonucleotides that reflect the sequences of the extreme termini of the viral long terminal repeats (LTRs). The results of gel filtration and a detailed binding density analysis indicate that the integrase binds to the LTR as a high-order oligomer at a density equivalent to 10 +/- 0.8 integrase monomers per 21-base pair LTR. The corresponding binding isotherm displays a Hill coefficient of 2, suggesting that the binding mechanism involves the cooperative interaction between two oligomers. This interaction is quite stable, exhibiting a prolonged half-life (t1/2 approximately 13 h) in the presence of Mn2+ cations. Complexes were less stable when formed with Mg2+ (t1/2 approximately 1 h). The role of Mn2+ appears to be in the induction of the protein-protein interactions that stabilize the bound complexes. In terms of the 3'-end processing of the LTR, similar catalytic rates (kcat approximately 0.06 min-1) were obtained for the stable complex in the presence of either cation. Hence, the apparent preference observed for Mn2+ in standard in vitro integration assays can be attributed entirely to the augmentation in the DNA binding affinity of the integrase.