1. The non-steady-state turnover of low-density lipoprotein (LDL), labelled in its apoprotein moiety (apo-B) with 131I, was determined in four patients with familial hypercholesterolaemia, three of them homozygotes.
2. The fractional and absolute catabolic rates (FCR and ACR) of LDL-apo-B were determined by relating the excretion of radioactivity, measured in urine in vitro and by whole-body counter in vivo, to plasma radioactivity and to LDL specific radioactivity respectively.
3. The FCR remained relatively constant, even after marked reduction of LDL pool size by means of plasma exchange. This confirms the existence of an intrinsic defect in LDL catabolism in familial hypercholesterolaemia.
4. LDL-apo-B synthesis, determined by summing the ACR and the daily increment in plasma LDL, was much higher in the three homozygotes than in the one heterozygote, in whom the synthetic rate was normal.
5. These results illustrate the usefulness of combining plasma exchange and whole-body radioactivity counting as a means of examining the relationship between the turnover and pool size of a 131I-labelled protein, such as LDL.