Nutritional science is developing from the calculation of requirements toward prediction of responses to nutrients. Responses are defined as the consequences of the animal's interaction with its feed and other aspects of its environment For dairy cows the important responses to predict are yields of major milk constituents (fat, protein, and lactose), rates of changes of body fat and protein, and voluntary feed consumption. In order to make predictions of cow responses, equal weight needs to be given to quantitative descriptions of cow characteristics, feed characteristics, and relevant aspects of the environment. This paper presents a framework that allows quantitative descriptions of these various attributes to be combined for the purposes of response prediction. The nutrients of importance are those major end products of digestion, which act as substrates for the generation of animal products. Quantitative aspects of genotype include description of potential milk constituent yield, mature body size and composition, and rate of maturing, including a description of “labile” protein mass and animal capacities for ingestion of potentially constraining feed attributes. A variety of approaches is available to simulate nutrient supply and use for purposes of response prediction. The synthesis of such models adds both intellectual richness to the process of developing nutritional science and improved frameworks for testing theories through experiment.