The defective parvovirus Adeno-associated virus (AAV) is absolutely dependent upon coinfection with either Adenovirus or Herpes Simplex Virus (HSV) for its multiplication. We have compared the terminal repeats of HSV-1F strain DNA with the terminal 200 nucleotides of AAV DNA. Our findings demonstrate similarities between portions of the HSV inverted repeats found at the L/S junction and the termini of AAV. By computer analysis we have determined potential secondary folding patterns for both genomes. The following points can be made about the a, b, and c repeats in HSV: (1) Regions b and c are complementary over a significant portion of their length. (2) The ends of a can fold back on themselves to form large secondary structures. Moreover, when the b and c homology is used to align the ends of a, the b/a and c/a junctions are within 1 base of each other. (3) The short direct repeats within a are essentially a large loop with little secondary structure. The potential implications of this structure are discussed and a model for HSV DNA replication is presented.