Lipoproteins are currently being recognized as transport vehicles for lipophilic drugs and xenobiotic chemicals in plasma. The weight of in vitro evidence suggests lipoproteins as the principal carries of 2,4,5, 2',4',5'-hexachlorobiphenyl (6-CB) in plasma from normolipidemic rats and humans. The present study examined the in vivo distribution of 6-CB among lipoproteins as well as the influence of time on the absolute amount and proportion of 6-CB associated with each density fraction. Plasma obtained between 1 min and 24 hr after an iv injection of 6-[14C]CB was separated into very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) fractions by sequential ultracentrifugation. The in vivo results corroborate the in vitro data which suggest LDL to be a major transport vehicle for 6-CB in plasma. However, the preference of 6-CB for LDL existed for only a short time following injection. From 6 to 24 hr after administration of 6-CB, there was a shift in the distribution of the PCB from LDL to HDL and the remaining protein-rich bottom fraction. By 24 hr, the proportion of 6-CB in LDL had declined from 80% of the plasma concentration to 30%, while that in HDL had doubled. Furthermore, the amount of 6-CB in the bottom fraction accounted for 35% of the radioactivity in plasma at 24 hr as opposed to less than 5% up to 1 hr after administration. The absolute contents of 6-CB in both HDL and the bottom fraction also increased during the later time points. Analysis of the decay curves of 6-CB among the various lipoproteins further substantiated a change in the distribution of 6-CB over time. The decay of 6-CB in LDL most closely resembled its disappearance from plasma. The content of 6-CB remaining in plasma at 24 hr was equally distributed among LDL, HDL, and the bottom fraction. Changes in lipoprotein composition during the 24-hr period could not explain 6-CB redistribution, since there were no significant differences in the proportion of constituents comprising VLDL, LDL, HDL, or the bottom fraction.