Dietary intervention is the first and usually successful approach in the treatment of high LDL cholesterol (LDL-C) concentration, but it is frequently accompanied by a decrease in HDL concentration. We studied 14 male volunteers on two different diets, high saturated fatty acid (SFA) and high PUFA, in a crossover design to test whether a decrease in HDL can affect reverse cholesterol transport from relabeled macrophages. A significant decrease of LDL-C (in mmol/l) after a PUFA diet compared with an SFA diet from 3.15 +/- 0.65 to 2.80 +/- 0.56 (P < 0.01) was accompanied by a significant decrease of HDL cholesterol (HDL-C) (in mmol/l) from 1.21 +/- 0.30 to 1.10 +/- 0.32 (P < 0.05). These changes did not affect cholesterol efflux (CHE) from macrophages (9.74 +/- 1.46% vs. 9.53 +/- 1.41%). There was no correlation between individual changes of HDL-C and changes of CHE. It is concluded that the decrease of HDL-C after successful dietary intervention of LDL-C is not accompanied by a decrease of CHE.