Investigating the feasability and application appropriate to determination of lipoprotein turnover, 75Se-selenomethionine (Se-M) incorporation in lipoproteins was studied in eight hospitalized patients. Three were hyperlipidemic diabetic subjects (HL), and five were normolipidemic but otherwise abnormal subjects (NL). Maximum activity was observed in the VLDL fraction within 2-3 hr, and was followed by a biexponential decay. Incorporation into the LDL-I (density, 1.006-1.019 mug/ml) occurred at a rate which correlated with the rapid decay rate of the VLDL Se-M activity. The decay of the Se-M was single exponential in the LDL-I and LDL-II (density, 1.019-1.063 mug/ml), suggesting undirectional transfer of the label. The HDL fraction showed a rapid initial Se-M uptake which was followed by a slow rise, resulting in a complex time-activity curve. The Se-M activity was significantly higher in the VLDL fraction and slightly lower in the LDL and HDL fractions in the HL as compared to the NL subjects. The VLDL-apoprotein concentration increased by a significantly greater amount in the HL (374 mug/ml) than in the NL subjects (67 mug/ml). There was a significant increase in VLDL-apoprotein turnover in the presence of a fractional turnover rate that was not significantly lower in the three hyperlipidemic subjects compared to the NL controls. In vivo 75Se-selenomethionine labeling allows the estimation of the synthesis and removal rate of apoproteins.