Maintaining a high degree of spatial resolution in proton computed tomography (pCT) is a challenge due to the statistical nature of the proton path through the object. Recent work has focused on the formulation of the most likely path (MLP) of protons through a homogeneous water object and the accuracy of this approach has been tested experimentally with a homogeneous PMMA phantom. Inhomogeneities inside the phantom, consisting of, for example, air and bone will lead to unavoidable inaccuracies of this approach. The purpose of this ongoing work is to characterize systematic errors that are introduced by regions of bone and air density and how this affects the accuracy of proton CT in surrounding voxels both in terms of spatial and density reconstruction accuracy. Phantoms containing tissue- equivalent inhomogeneities have been designed and proton transport through them has been simulated with the GEANT 4.9.0 Monte Carlo tool kit. Various iterative reconstruction techniques, including the classical fully sequential algebraic reconstruction technique (ART) and block-iterative techniques, are currently being tested, and we will select the most accurate method for this study. © 2009 American Institute of Physics.