The purpose of this review is to outline and interpret the effects of nutrition, physiological state, sex, genetics, and age on composition of the fat-free dry matter of birds, mammals, and fishes in order to test the hypothesis that the protein:ash ratio in the body is constant. Calculations from a broad array of published data revealed that nutritional factors, including mineral, protein and amino acid nutriture, frequency and level of feeding, and energy intake and nonnutritional factors, including physiological state, sex, genetic background, and age of animal, may each alter the ratio of protein:ash in the body. All or part of the response may be associated with changes in accretion of body protein and(or) skeletal development and mineralization imposed by these nutritional and nonnutritional factors. In most cases of amino acid or protein deficiency, the protein:ash ratio was decreased relative to the control because the deposition of protein in muscle and viscera was reduced more than the growth and mineralization of the skeleton. In other cases, the protein:ash ratio was increased relative to a control because the dietary Ca or P intake or absorption limited skeletal mineralization. More knowledge is needed of how skeletal development and protein:ash ratio in the body is regulated, especially under the influence of nutritional, ontogenetic, and physiological variables among different genotypes of mammals, birds, and fishes. Documentation that the protein:ash ratio in the whole body of representative mammals, birds, and fishes is not constant, but is subject to manipulation, has important physiological and economic implications for developing food animals for the efficient production of lean meat.