In this review, we discuss the mechanismsof responses of various tissues of the lactating dairy cow, particularly the mammary glands, to perturbations in supply of single amino acids that result in observed milk protein yields. Additions of methionine, lysine, histidine or leucine to the absorptive supply cause arterial concentrations of these amino acids to increase, mammary extractions to drop and mammary blood flow to decrease. Single subtractions of essential amino acids have the opposite effect. Changes in mammary blood flow that have been recorded can be explained as attempts by the mammary glands to restore intracellular ATP balance in the face of altered concentrations of energy metabolites in the general circulation. In a quantitative sense, milk protein yield is relatively insensitive to fluctuations in arterial amino acid concentrations but can be stimulated by any one of a number of amino acids. In this context, it is suggested that the designation of a limiting amino acid is not appropriate to the purpose of predicting milk protein yield. Rather, milk protein synthesis appears to operate at a predetermined rate set by external communications of milk withdrawal rate, physiological state and overall nutritional status. Utilization of amino acids (AA) by splanchnic and peripheral tissues, in coordination with the mammary setpoint, offsets imperfections in the dietary AA supply. How strongly an individual AA influences the mammary setpoint, arterial concentrations of energy metabolites, and mammary AA transport capacity will determine the magnitude of the milk protein yield response when its absorptive supply is changed. Key words: Dairy cows, milk protein, amino acid