We tested whether nutrient intakes estimated from 4-d diet records were associated with plasma lipoprotein subclasses in 103 men who were randomly assigned to a low-fat (24% fat) and a high-fat (46% fat) diet for 6 wk each in a crossover design. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities were also determined in a subset of 43 men. Changes in intake (ie, high fat minus low fat) of total saturated fatty acids, as well as myristic (14:0) and palmitic (16:0) acids, were positively correlated (P < 0.01) with increases in mass of large LDL particles [measured by analytic ultra-centrifugation as mass of lipoproteins of flotation rate (Sf) 7-12] and with LDL peak particle diameter and flotation rate, but not with changes in LDL-cholesterol concentration. Changes in total saturated fatty acids as well as myristic and palmitic acids were also inversely associated with changes in HL activity (P < 0.05). With the high-fat diet only, variation in dietary total saturated fatty acid intake was inversely correlated (P < 0.01) with concentrations of small, dense LDL of Sf 0-5. This correlation was significant specifically for myristic acid (P < 0.001). Stearic acid (18:0), monounsaturates, and polyunsaturates showed no significant associations with lipoprotein concentrations. These data indicate that a high saturated fat intake (especially 14:0 and 16:0) is associated with increased concentrations of larger, cholesterol-enriched LDL and this occurs in association with decreased HL activity.