The purpose of this study was to determine the relationship between changes in maximal oxygen uptake (V̇O2 max) and submaximal markers of aerobic fitness and changes in risk factors for cardiovascular disease (CVD) and non-insulin-dependent diabetes mellitus (NIDDM) consequent to a 20-week endurance training program. The 502 participants in this study were healthy and previously sedentary men (n = 250) and women (n = 252) of varying age (17 to 65 years) and race (blacks n = 142; whites n = 360) who had completed the HERITAGE Family Study testing and training protocol. Following baseline measurements, participants trained on cycle ergometers 3 days/week for a total of 60 exercise sessions starting at the heart rate (HR) associated with 55% of V̇O2 max for 30 minutes/session. This was progressively increased to the HR associated with 75% of V̇O2 max for 50 minutes/session, which was maintained during the last 6 weeks. V̇O2 max, heart rate at 50 W, power output at 60% of VO2 max, lipids and lipoproteins, resting blood pressure, body composition including abdominal fat (computed tomography [CT] scan), and blood glucose and insulin at rest and at peak following an intravenous glucose tolerance test (IVGTT) were determined both before and after training. Following training, there were significant increases in V̇O2 max (16%) and the power output at 60% of VO2 max and a significant decrease in HR at 50 W. These changes in markers of aerobic fitness were significantly correlated only to the changes in the body composition variables and the lipids and lipoproteins. Further, there was considerable individual variation in response for all variables studied. Finally, when risk factor data were analyzed by quartile of change in V̇O2 max, there were few significant relationships. It is concluded that there is a significant relationship between changes in markers of aerobic fitness and changes in several risk factors for CVD and NIDDM. However, the magnitude of these relationships is small.