Purpose: The purpose of this study was to determine the magnitude of changes in cardiac output (Qc), stroke volume (SV), and arterial-mixed venous oxygen difference (a-v̄O2 diff) during submaximal exercise following a 20-wk endurance training program, with the primary focus on identifying differences in response by race, sex, and age. Methods: The participants in this study (N = 631) were healthy and previously sedentary men (N = 277) and women (N = 354) of varying age (17-65 yr) and race (blacks, N = 217; whites, N = 414) who had completed the HERITAGE Family Study protocol. After baseline measurements, participants trained on cycle ergometers 3 dwk-1 for a total of 60 exercise sessions starting at the HR associated with 55% of maximal oxygen uptake (V̇O2max) for 30 min/session and building to the HR associated with 75% of V̇O2max for 50 min/session, which was maintained during the last 6 wk. HR, Qc (CO2 rebreathing), and SV (Qc/HR) were determined in duplicate at 50 W and at 60% of VO2max on two different days both before and after training. Results: After training, there were significant decreases in HR and Qc, and significant increases in SV and a-v̄O2 diff at 50 W (except for no change in a-v̄O2 diff in black men). The changes in HR differed by sex and age, and the changes in SV, Qc, and a-v̄O2 diff differed by race. Qc decreased by 0.6 Lmin-1 at 50 W for the total sample, consistent with the decrease in V̇O2 at this power output. At 60% of V̇O2max, HR decreased, and SV, Q, and a-v̄O2 diff increased. There were small differences in response by sex (HR and SV), race (HR), and age (HR and Qc). Conclusion: It is concluded that the cardiovascular systems of men and women, blacks and whites, and younger and older subjects are not limited in their ability to adapt to endurance training.