BACKGROUND: Disease maps are used increasingly in the health sciences, with applications ranging from the diagnosis of individual cases to regional and global assessments of public health. However, data on the distributions of emerging infectious diseases are often available from only a limited number of samples. We compared several spatial modelling approaches for predicting the geographic distributions of two tick-borne pathogens: Ehrlichia chaffeensis, the causative agent of human monocytotropic ehrlichiosis, and Anaplasma phagocytophilum, the causative agent of human granulocytotropic anaplasmosis. These approaches extended environmental modelling based on logistic regression by incorporating both spatial autocorrelation (the tendency for pathogen distributions to be clustered in space) and spatial heterogeneity (the potential for environmental relationships to vary spatially). RESULTS: Incorporating either spatial autocorrelation or spatial heterogeneity resulted in substantial improvements over the standard logistic regression model. For E. chaffeensis, which was common within the boundaries of its geographic range and had a highly clustered distribution, the model based only on spatial autocorrelation was most accurate. For A. phagocytophilum, which has a more complex zoonotic cycle and a comparatively weak spatial pattern, the model that incorporated both spatial autocorrelation and spatially heterogeneous relationships with environmental variables was most accurate. CONCLUSION: Spatial autocorrelation can improve the accuracy of predictive disease risk models by incorporating spatial patterns as a proxy for unmeasured environmental variables and spatial processes. Spatial heterogeneity can also improve prediction accuracy by accounting for unique ecological conditions in different regions that affect the relative importance of environmental drivers on disease risk.