To improve the antisense activity of AS ODN (antisense oligodeoxynucleotide), a conjugate covalently linked to DOX (doxorubicin) at its 3'-end was synthesized and its antisense activity in human carcinoma DOX-resistant cells (KB-A-1) was investigated in vitro. The intracellular DOX concentration in KB-A-1 cells treated with the conjugate was detected in vitro by HPLC. Results showed that the intracellular DOX concentration was 6.4-fold higher in KB-A-1 cells treated with the conjugate when compared with that in the cells treated with DOX alone. In contrast, a 1.8-fold increase in the concentration of DOX was observed when the cells were treated with AS ODN. Reverse transcriptase PCR and Western-blot analysis showed a more significant decrease in the amount of mdr1 (multidrug resistance 1 gene) mRNA and P-glycoprotein in KB-A-1 cells. Chemosensitivity of KB-A-1 cells to DOX was also investigated in vitro. When the cells were first exposed to the conjugate (0.5 microM) for 24 h and then exposed to DOX for 24 h, the IC(50) value of DOX decreased from 21.5 to 2.2 microM, whereas the IC(50) value of DOX decreased only to 16.8 microM when the cells were treated with the mixture of the same concentration of AS ODN. These results suggest that the conjugate is effective in reversing multidrug resistance. Further studies will be conducted to explore the effect of the conjugate on tumours in vivo.