The net transfer of labeled alpha-tocopherol from donor to acceptor lipoproteins at physiological concentrations was investigated. Labeled lipoproteins were isolated i) following in vitro addition of [3,4-3H] all rac-alpha-tocopherol to plasma, or ii) from plasma obtained 12-16 h after ingestion by normal subjects of an oral dose (100 mg each) of 2R,4'R,8'R-alpha-[5,7-(C2H3)2]tocopheryl acetate and 2S,4'R,'R-alpha-[5-C2H3]tocopheryl acetate. A constant amount (on a protein basis) of labeled lipoprotein was incubated with an increasing amount of unlabeled acceptor lipoprotein for 2 h at 37 degrees C. No discrimination between stereoisomers of alpha-tocopherol was detected. Labeled VLDL and labeled LDL (very low and low density lipoproteins, respectively) tended to retain their labeled tocopherol. Labeled high density lipoproteins (HDL) readily transferred the labeled tocopherol to VLDL (> 60% transferred), while the transfer to LDL was dependent upon the ratio of labeled HDL/LDL with a lower net transfer at higher ratios. This dependency of the distribution of tocopherol upon the ratio of HDL/LDL was also observed in vivo. The tocopherol/mg HDL protein was measured in 11 subjects with varying HDL levels. As the % HDL in the plasma increased from 14 to 50%, the tocopherol/HDL protein also increased (r2 = 0.37, P < 0.05).