Liposomalcis-bis-neodecanato-trans-R,R-1,2-diaminocyclohexaneplatinum (11) (L-NDDP) is a liposome-entrapped platinum complex that has shown partial lack of cross-resistance with cisplatin in human colon carclnoma LoVo cells. We studied the drug accumulation and DNA damage induced by L-NDDP and cisplatin in LoVo and LoVo/PDD cells. Our results indicate that the accumulation of L-NDDP in LoVo cells is several-fold higher than that of cisplatin; that the accumulation of L-NDDP is simillar in both cell lines, whereas that of cisplatin is reduced by 2− to 3-fold in LoVo/PDD cells; and that the transmembrane transport of cispiatin is highly dependent on temperature while that of L-NDDP is not. We also found that the cytotoxicity of both agents correlates with the extent of DNA–protein cross-link formation, and that DNA interstrand cross-linking does not appear to play a role in the cytotoxicity of L-NDDP, whereas it correlates with clsplatin cytotoxicity.