The monoclonal antibody-vinca alkaloid conjugate, KS1/4-DAVLB (LY256787), and free 4-desacetylvinblastine (DAVLB) were administered i.v. to male athymic nude mice bearing P3/UCLA human lung adenocarcinoma tumors. Although the plasma pharmacokinetics were similar between LY256787 and DAVLB (terminal plasma half-lives of 62 and 83 hr, respectively), substantial differences in the volumes of distribution and initial redistribution-elimination phases were found. Uptake of LY256787 into tumor was apparent, with maximal radioequivalent concentrations measured 96 hr after dosing; no similar uptake was found after dosing with free DAVLB. The ratios of concentrations of drug radioequivalents in tumor to those in other tissues were generally greater than 1.0 when measured 24 to 48 hr after dosing with LY256787 but were less than 1.0 after free DAVLB. These data support the concept of site-specific delivery to the tumor tissue of the vinca alkaloid by the antibody. Plasma pharmacokinetics and tissue distribution were compared in males and females with a lower dose of LY256787. No sex-related differences in the plasma pharmacokinetics were found (terminal half-lives of 90 and 84 hr in males and females). Some sex-related biodistribution differences occurred. In all studies, the primary route of elimination was fecal. These studies suggest that the KS1/4 monoclonal antibody targets DAVLB to the P3/UCLA human lung adenocarcinoma in vivo in the human xenograft model and that an increased therapeutic index may be achieved with LY256787 over conventional free drug therapy.