This study was conducted to test whether cortical activation varies across successive epoques during functional magnetic resonance imaging (fMRI) studies. Ten normal adult volunteers were studied with a 1.5-T MR scanner. Pseudocoronal study planes were chosen perpendicular to the tentorium cerebelli, at two thirds the distance from the posterior edge of the splenium of the corpus callosum to the transverse sinuses. Functional images were acquired with a T2*-weighted spoiled gradient echo sequence. The visual cortex was stimulated by goggles flashing at 8 Hz. Each study consisted of 82 sequential scans, lasting 15 seconds each for a total of 20.5 minutes. Two scans without stimulation were alternated with two scans of visual stimulation. Scans 3 through 83 were divided into five sequences of 16 scans. For each sequence, the number of pixels within a predefined rectangular region of interest that showed increased activity during stimulation were counted. Least squares regression models of straight lines were fit to the data. The initial level of visual cortex activation in the region of interest, as measured by the y-intercept, varied substantially from subject to subject (range: 4-68, p < 0.001). There was sufficient evidence of systematic change with time to reject the hypothesis of constant activation with the same stimulus over time (p=0.02). The observed visual cortex activation with single-plane fMRI varied both with time over successive epoques and among subjects. Possible factors responsible for the variation may include head movement, eyelid position, attention, and physiologic fatigue. These factors must be accounted for in experimental design and in data analysis and interpretation.