Physiological studies of long-term cardiovascular adaptation to exercise require training regimens that give robust conditioning effects and adequate testing procedures to quantify the outcome. We developed a valid and reproducible protocol for measuring maximal oxygen uptake (VO(2 max)), which was reached at a 25 degrees inclination with a respiratory exchange ratio > 1.05 and blood lactate > 6 mmol/l. The effect of intensity-controlled aerobic endurance training was studied in adult female and male rats that ran 2 h/day, 5 days/wk, in intervals of 8 min at 85-90% of VO(2 max) and 2 min at 50-60% of VO(2 max), with adjustment of exercise level according to VO(2 max) every week. After 7 wk, the increase in VO(2 max) plateaued at 60-70% above sedentary controls. Ventricular weights and myocyte length were up 25-30% and 6-12%, respectively. Work economy, oxygen pulse, and heart rate were sufficiently changed to indicate substantial cardiovascular adaptation. The model mimics important human responses to training and could be used in future studies on cellular, molecular, and integrative mechanisms of improved cardiovascular function.