Serum clearance kinetics of murine senile amyloid-related high-density lipoprotein (HDL) apoprotein A-II (apo A-II) was examined in the senescence-accelerated mouse, prone (SAM-P/1) and resistant (SAM-R/1), with 125I-HDL purified from both strains. In SAM-R/1, with 125I-HDL purified from both strains. In SAM-R/1, the serum half-life of apo A-II was not altered with increasing age and was practically identical to that of apo A-I. In 2-month old SAM-P/1, the serum half-life of both apo A-I and apo A-II was generally the same as observed in SAM-R/1. However, at age 6 and 12 months, in SAM-P/1, the serum half-life of apo A-II decreased significantly and was less than that of apo A-I. These age-related changes in apo A-II clearance kinetics were observed regardless of the HDL donor. The authors also examined the tissue distribution of injected apo A-II, using 125I-apo A-II reconstituted HDL, and found that several organs trapped more 125I radioactivity in old SAM-P/1 than in young mice. This evidence strongly suggests that age-related changes in the metabolic environment of apo A-II might affect senile amyloidogenesis in SAM-P/1.