The results from a single functional magnetic resonance imaging session are typically reported as indicative of the subject's functional neuroanatomy. Underlying this interpretation is the implicit assumption that there are no responses specific to that particular session, i.e., that the potential variability of response between sessions is negligible. The present study sought to examine this assumption empirically. A total of 99 sessions, comprising 33 repeats of simple motor, visual, and cognitive paradigms, were collected over a period of 2 months on a single male subject. For each paradigm, the inclusion of session-by-condition interactions explained a significant amount of error variance (P < 0.05 corrected for multiple comparisons) over a model assuming a common activation magnitude across all sessions. However, many of those voxels displaying significant session-by-condition interactions were not seen in a multisession fixed-effects analysis of the same data set; i.e., they were not activated on average across all sessions. Most voxels that were both significantly variable and activated on average across all sessions did not survive a random-effects analysis (modeling between-session variance). We interpret our results as demonstrating that correct inference about subject responses to activation tasks can be derived through the use of a statistical model which accounts for both within- and between-session variance, combined with an appropriately large session sample size. If researchers have access to only a single session from a single subject, erroneous conclusions are a possibility, in that responses specific to this single session may be claimed to be typical responses for this subject.