A regression approach was used to assess quantitatively the influence of lysine and ME intake during lactation on yield of milk components and to determine whether this influence was mediated through precursor metabolite concentrations in the blood. The influence of lysine and energy intake on sow weight and backfat loss also was analyzed by linear regression. Twenty-three primiparous Landrace x Yorkshire sows were fed one of nine corn-soybean meal diets to achieve a matrix of lysine (15, 30, or 45 g/d) and ME (6.5, 11.5, or 16.5 Mcal/d) intakes. Sow BW and backfat losses were found to be predominantly controlled by ME intake (P less than .02), with no response to lysine intake (P greater than .92). Lysine and ME intake explained a smaller portion of the variability in milk component yield on d 8 (R2 less than .34) than on d 22 (R2 = .64 to .78), evidence that dietary effects of milk production increased as lactation progressed. Lysine and ME intake had an interactive influence (P less than .05) on yield of all milk components except lactose, demonstrating that the amount of lysine required to maximize milk production increased as ME intake increased. Strong relationships between diet and most blood precursor metabolite concentrations (R2 = .5 to .7) were detected on d 22. No obvious relationships between precursor metabolite concentrations and milk component yield (R2 = .05 to .2) were observed. These results describe quantitatively the prominent interactive effects of lysine and ME intake on yield of milk components and demonstrate that these effects are not directly associated with changes in precursor pool concentrations.