Covariance analyses of positron emission tomography (PET) data are used increasingly to elucidate the functional connectivity between brain regions during different cognitive tasks. Functional connectivity may be estimated by examining the covariance between regions over time or across subjects. In functional brain-mapping studies, across-subjects covariance matrices derived from within-task (nonsubtracted) and between-task (subtracted) data characterize different, complementary aspects of functional interactions. The authors study amygdala-orbitofrontal interactions during three task conditions (aversive olfaction, odor detection, and resting with eyes closed) to illustrate the strengths and limitations of across-subjects covariance analyses based on subtracted and nonsubtracted data. This example underscores the dynamic nature of connectivity between the amygdalae and orbitofrontal cortices and highlights the importance of including data from resting conditions in covariance analyses.