In order to identify the optimal target sites for antisense oligonucleotides in the human multiple drug resistance mRNA, the secondary structure of the 5′-terminal part of this mRNA (nucleotides 1–678) was investigated. By using results of probing with ribonucleases T1, ONE and V1 and results of computer simulations, a model of the 5′-region of the PGY1/MDR1 mRNA was built. The molecule is formed by three major domains comprising several hairpins separated by single-stranded fragments. The predicted single-stranded regions of the PGY1/MDR1 mRNA efficiently bind complementary oligonucleotides.