Plasma high density lipoproteins (HDL) and their major protein, apolipoprotein (apo) A-I, are deficient in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits. As the pathophysiology of subnormal HDL-apo A-I is unclear, we examined kinetic parameters of HDL-apo A-I in WHHL rabbits and normolipidemic Japanese White (control) rabbits. The total plasma mass of HDL-apo A-I was significantly smaller (P less than 0.01) in WHHL rabbits than in controls (less than one-third). Mean fractional catabolic rates (FCR) computed from the specific radioactivity decay curves of HDL-apo A-I were significantly greater (P less than 0.01) in WHHL rabbits than in controls (0.874 +/- 0.052 vs. 0.502 +/- 0.060/day, respectively). Mean synthetic rates of HDL-apo A-I were significantly lower (P less than 0.01) in WHHL rabbits than in controls (8.67 +/- 0.59 vs. 18.14 +/- 3.75 mg/kg body weight/day, respectively). We conclude that the deficiency of plasma HDL-apo A-I in the WHHL rabbits resulted from an increase in FCR and a decrease in apo A-I synthesis.