The Tn21 subgroup of class II transposons plays an important role in the dissemination of resistance genes and especially in the epidemic spread of multi-resistance. This ability reflects the variety of resistance genes that associate with the streptomycin/spectinomycin-resistance gene (aadA) of Tn21. Deletion experiments with Tn2426, a typical member of the Tn21 subgroup, and sequencing of the region that accommodates additional resistance genes revealed significant structural characteristics. Each resistance gene was flanked by short, directly repeated recombinationally active sequences with unexpected variability in their sequence and length. The consensus for a recombinationally active sequence appeared to be 13 bp in length (TAAAACAANGNNA), compared to previous estimates of 54 bp. This sequence, in combination with the product of the integrase gene, is responsible for the genetic variability of members of the Tn21 family of transposable elements and the dissemination of multi-resistance.