Forty-two healthy men and women were subjected to four consecutive dietary periods differing in the fat content of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (n-6) [PUFA(n-6)] and (n-3) [PUFA(n-3)]. Plasma lipids, vitamin E, and in vitro LDL oxidation were examined during each period. Adhesion of human monocytes to cultured human endothelial cells was used as a functional test to identify differences in the biological properties of LDL from each dietary period. Consumption of an SFA-rich diet resulted in higher LDL cholesterol (4.06 +/- 0.85 mmol/L, P < .05) than did consumption of MUFA- (3.59 +/- 0.75 mmol/L), PUFA(n-6)- (3.44 +/- 0.77 mmol/L), or PUFA(n-3)- (3.31 +/- 0.8 mmol/L) rich diets. HDL cholesterol was lower during both PUFA-rich diets (1.24 +/- 0.28 and 1.27 +/- 0.28 mmol/L for n-6 and n-3, respectively) than during the SFA-(1.32 +/- 0.36 mmol/L) and MUFA- (1.32 +/- 0.34 mmol/L) rich diets. LDL resistance to copper-induced oxidation, expressed as lag time, was highest during the MUFA-rich diet (55.1 +/- 7.3 minutes) and lowest during the PUFA(n-3)- (45.3 +/- 7 minutes) and SFA- (45.3 +/- 6.4 minutes) rich diets. LDL induction of monocyte adhesion to endothelial cells was lower during the MUFA-rich diet than the other periods. The highest monocyte adhesion was obtained during the PUFA(n-3) and SFA dietary periods. In conclusion, an MUFA-rich diet benefits plasma lipid levels compared with an SFA-rich diet. Furthermore, this diet results in an increased resistance of LDL to oxidation and a lower rate of monocyte adhesion to endothelial cells than the other dietary fats examined.