Background Gait training robots should display a minimum added inertia in order to allow normal walking. The effect of inertias in specific directions is yet unknown. We set up two experiments to assess the effect of inertia in anteroposterior (AP) direction to the ankle and AP and mediolateral (ML) direction to the pelvis. Methods We developed an experimental setup to apply inertia in forward backward and or sideways directions. In two experiments nine healthy subjects walked on a treadmill at 1.5 km/h and 4.5 km/h with no load and with AP loads of 0.3, 1.55 and 3.5 kg to the left ankle in the first experiment and combinations of AP and ML loads on the pelvis (AP loads 0.7, 4.3 and 10.2 kg; ML loads 0.6, 2.3 and 5.3 kg). We recorded metabolic rate, EMG of major leg muscles, gait parameters and kinematics. Results & discussion Adding 1.55 kg or more inertia to the ankle in AP direction increases the pelvis acceleration and decreases the foot acceleration in AP direction both at speeds of 4.5 km/h. Adding 3.5 kg of inertia to the ankle also increases the swing time as well as AP motions of the pelvis and head-arms-trunk (HAT) segment. Muscle activity remains largely unchanged. Adding 10.2 kg of inertia to the pelvis in AP direction causes a significant decrease of the pelvis and HAT segment motions, particularly at high speeds. Also the sagittal back flexion increases. Lower values of AP inertia and ML inertias up to 5.3 kg had negligible effect. In general the found effects are larger at high speeds. Conclusions We found that inertia up to 2 kg at the ankle or 6 kg added to the pelvis induced significant changes, but since these changes were all within the normal inter subject variability we considered these changes as negligible for application as rehabilitation robotics and assistive devices.