Large individual differences in the responsiveness of cardiorespiratory fitness (VO2peak) to endurance training have been observed in healthy subjects. We tested the hypothesis that subjects with a poor responsiveness to endurance training might benefit from resistance training in terms of aerobic fitness. The study population consisted of sedentary healthy male and female subjects (n=91, 42+/-5 year) assigned to either a training (n=73) or a control group (n=18). The randomized cross-over study design included a 2-week laboratory-controlled endurance or resistance training period with a 2-month detraining period between the interventions. Large individual differences were observed in the changes of VO2peak (DeltaVO2peak) after both the endurance (average 8+/-6 %, P<0.001, range -5 to +22%) and resistance training (average 4+/-5%, P<0.001, range -8 to +16%). The average increase in DeltaVO2peak between genders was similar after both the endurance (8+/-6% for both genders, P=ns) and resistance training (3+/-5% for males and 5+/-6% for females, P=ns). There was no linear relationship between the changes in VO2peak after each training intervention (r=-.09, P=ns). On the contrary, when the study group was divided into quartiles according to the endurance training response (1+/-3, 6+/-1, 9+/-1, and 16+/-3% increase in VO2peak), the group with the lowest response to endurance training increased VO2peak after the resistance training intervention (DeltaVO2peak 7+/-5%, P<0.001). The individual responsiveness of VO2peak to exercise training is related to the mode of training. The healthy males and females whose training response is low after endurance training seem to result in a marked improvement in their cardiorespiratory fitness by resistance training.