Apolipoprotein E (apoE) circulates as a mixture of sialilated and asialilated forms. In this study the catabolic fate and the plasma turnover rate of the different apoE forms have been investigated in vivo in humans. Asialo apoE (E) and doubly sialiated apoE (Ess) were isolated by preparative isoelectrofocusing from the VLDL of subjects homozygous for the E3 allele. 131E3 and 125E3ss were injected simultaneously into three hypertriglyceridemic subjects, and plasma samples were collected up to the sixth day. VLDL were isolated by ultracentrifugation, and the apoE forms were separated by isoelectrofocusing. Gel bands corresponding to E3 and E3ss were cut out and counted for the associated radioactivity. Residence times in plasma for 131E3 and 125E3ss were 0.95 ± 0.16 and 0.74 ± 0.16 days, respectively. As determined from the gel count distribution up to 24 hours, no conversion of the injected sialilated form to the correspondent asialilated form was detected.