To test the hypothesis that diet may exert differential effects on apolipoprotein (apo) A-I--containing high-density-lipoprotein (HDL) particles with (w) and without (w/o) apo A-II [Lp(A-I w A-II) and Lp(A-I w/o A-II)], the effects of a diet low in saturated fatty acids and cholesterol [National Cholesterol Education Panel (NCEP) Step 2 diet] on these lipoproteins were determined in eight normolipidemic subjects, aged 53-74 y, in both the fasting and nonfasting states. Compared with a diet high in saturated fatty acid and cholesterol, consumption of an NCEP diet (6 mo) lowered fasting plasma, low-density-lipoprotein, and HDL cholesterol, and nonfasting plasma cholesterol, triglyceride, and HDL cholesterol (P < 0.05- < 0.005). Phospholipid in fasting and nonfasting Lp(A-I w A-II) and Lp(A-I w/o A-II) was lower during the NCEP diet (P < 0.05-0.001), but reductions in apo A-I or A-II were observed only in Lp(A-I w A-II). In contrast, differences in particle-size profiles were detected in Lp(A-I w/o A-II) but not in Lp(A-I w A-II). These observations provide further evidence that Lp(A-I w A-II) and Lp(A-I w/o A-II) are distinct metabolic entities.