The metallacarboranes (Et 2 C 2 B 4 H 4 )-TaCl 2 (C 5 H 5 ) (1), (Et 2 C 2 B 4 H 4 )NbCl 2 (C 5 H 5 ) (2), (Et 2 C 2 B 4 H 4 )TaCl 2 (C 5 Me 5 ) (3), [(Me 3 Si) 2 C 2 B 4 H 4 ]TaCl 2 (C 5 H 5 ) (4) and (Me 2 C 2 B 4 H 4 )-TaCl 2 (C 5 H 5 ) (5) are potent cytotoxic agents against suspended tumors, producing cell death in several tissue culture lines; for example, all were effective against murine L1210 lymphoid leukemia, and all except 5 against murine P388 lymphocytic growth. Human leukemic growth is also retarded since 1-4 were effective against Tmolt 3 cell leukemia, all except 4 against Tmolt 4 leukemia, and 1, 2, and 5 against HI-60 leukemia. Cytotoxicity was found towards HuT-8 lymphoma, THP-1 acute monocytic leukemia and suspended HeLa-S 3 uterine carcinoma. Some but not all of the complexes were active against Sk-2 melanoma and Mcf-7 breast effusion growth. Mode-of-action studies in P388 lymphocytic leukemia cells showed that de novo purine synthesis was inhibited; this inhibition reduces DNA and RNA syntheses. Purine synthesis was reduced by compounds 3 and 4 at the regulatory enzymes, i.e. phosphoribosyl pyrophosphate (PRPP) amidotransferase and dihydrofolate reductase. The agents lowered d[ATP] and d[CTP] pools, further reducing DNA synthesis. The complexes afforded DNA fragmentation leading to apoptosis, but this was not by a mechanism of nucleoside alkylation, intercalation between base-pairs or cross-linking of the DNA strands.