The relation between systolic meridional wall stress (WS) and velocity of circumferential fiber shortening (VcFc) is widely accepted as a preload-independent index of contractility, with a linear relation in most subjects older than 2 y. However, this relation seems to become different in infants and after administration of inotropic agents. We decided to study the nature of the stress-velocity relation by a cross-sectional assessment of the influence of age, low afterload, and increased contractility. Study subjects were 30 healthy infants, 32 healthy older children, and 35 asymptomatic older children after completion of anthracycline chemotherapy. WS and VcFc at rest were studied in these infants and children. WS and VcFc were also studied after dobutamine infusion in both groups of older children. Linear regression analysis of the stress-velocity relation showed parallel slopes between the older children at rest and the post anthracycline children after dobutamine. The regression lines between the infants at rest and the healthy older children after dobutamine were also parallel, but with a different and steeper slope compared with the former groups. When comparing the stress-velocity relation of the overall population at rest with the overall population after dobutamine, the resulting regression lines are curvilinear and parallel, with a steeper slope at low afterload. The stress-velocity relation in infants and after dobutamine, resulting in low afterload is different compared with the stress-velocity relation in older children at rest and at higher afterload. Data of the overall population at rest and after dobutamine suggest a curvilinear relation.