Three 1-beta-D-arabinofuranosylcytosine 5'-diphosphate-1,2-dipalmitins from L-, D-, and DL-alpha-dipalmitoylphosphatidic acids have been synthesized and their antitumor activity against two ara-C2 resistant L1210 lymphoid leukemia sublines in mice were evaluated. These new prodrugs of ara-C include ara-CDP-L-dipalmitin, ara-CDP-D-dipalmitin, and ara-CDP-DL-dipalmitin. The L and DL isomers produced significant increase in life span (greater than 400%) and four to five long-term survivors (greater than 45 days) out of six animals bearing ip implanted partially ara-C resistant L1210 subline [L1210/ara-C (I)], while the D isomer displayed a marginal activity (ILS 100-121%). In contrast, the L isomer was completely ineffective against deoxycytidine kinase deficient ara-C resistant L1210 subline [L1210/ara-C (II)]. However, the results demonstrate that the L and DL isomers of ara-CDP-dipalmitin are promising new prodrugs of ara-C with improved efficacy.