This study examined the relationship between work of breathing and estimated blood flow to and oxygen consumption by the respiratory muscles. Five subjects performed inspiratory loaded breathing and voluntary hyperpnea while ventilatory work, cardiac output, and oxygen consumption were measured. Blood flow to and oxygen consumption by the respiratory muscles were estimated by subtracting the resting from the working values of cardiac output the oxygen consumption, respectively. Loaded breathing increased cardiac output, but there was no significant correlation with work of breathing, while oxygen consumption was significantly correlated with work of breathing. During hyperpnea both cardiac output and oxygen consumption were correlated with work of breathing. Our results indicate that blood flow and oxygen consumption are increased in a regular pattern with increases in work of breathing. These results may be significant in estimating the demand of the respiratory muscles in disease and exercise.