Wheel excitations measured on a heavy commercial vehicle by driving it through extreme road operating conditions, are considered as inputs to perform dynamic response analysis in a simulated laboratory and computational environment. From initial modal analysis results using finite elements, critical vehicle frame rail locations are identified for dynamic laboratory strain measurements on a six poster road load simulator that employs dynamic wheel excitations as input. Dynamic stresses calculated from measured strain values are then compared with computationally obtained stress results on each of these locations. This study also points out all geometric locations and vibration modes that may affect the design behavior of the frame members under extreme road operating conditions. The results obtained from this work can be considered for further fatigue life prediction and design optimization of chassis frame rail assembly. © 2009 IOP Publishing Ltd.