Various amphiphilic heterodinucleoside phosphates have recently been synthesized in order to overcome drug resistance. These agents contain 5-fluorodeoxyuridine (5-FdUrd) and arabinofuranosylcytosine (Ara-C). We now investigated the action of two of these novel dimers (#2 and #10) in sensitive and 5-FdUrd/Ara-C cross-resistant H9 human lymphoma cells. The dimers were compared with 5-FdUrd and Ara-C for growth inhibition, apoptosis induction, and cell-cycle effects. No significant difference in the cytotoxicity of dimer #2 could be observed between sensitive and 5-FdUrd/Ara-C cross-resistant H9 cells (IC50 values of 220 nM and 200 nM, respectively), indicating that further studies with this compound are warranted.