Inhomogeneities in myocardial structure and action potential duration (APD) lead to dispersion of APD throughout the heart. APD gradients in the range of 20-125 ms/cm have been reported to produce functional block. In this study, a multicellular fiber model was used to examine the effect of structural and ionic inhomogeneities on the likelihood of premature stimuli to produce functional block. With the use of both the Fenton-Karma and Luo-Rudy phase II membrane models, functional block is found to occur in tissue with a maximum gradient <45 ms/cm and depends on the spatial extent. In general, the narrower the extent the larger the magnitude needed for block. A simple relationship for predicting block is presented that only requires information about the conduction velocity (CV) restitution properties of the tissue and the APD gradients. Analysis reveals that the effects of a steep CV restitution slope may be beneficial in overcoming intrinsic cellular heterogeneity for a single premature beat.