Event-related functional magnetic resonance imaging (ER-fMRI) involves the mapping of averaged hemodynamic changes resulting from repeated, brief (<3 sec) brain activation episodes. In this paper, two issues regarding constant-interstimulus interval ER-fMRI were addressed. First, the optimal interstimulus interval (ISI), given a stimulus duration (SD), was determined. Second, the statistical power of ER-fMRI relative to that of a blocked-design paradigm was determined. Experimentally, it was found that with a 2-sec SD, the optimal ISI is 12 to 14 sec. Theoretically, the optimal repetition interval (T(opt) = ISI + SD) is 12 to 14 sec for stimuli of 2 sec or less. For longer stimuli, T(opt) is 8 + 2 x SD. At the optimal ISI for SD = 2 sec, the experimentally determined functional contrast of ER-fMRI was only -35% lower than that of blocked-design fMRI. Simulations that assumed a linear system demonstrated an event-related functional contrast that was -65% lower than that of the blocked design. These differences between simulated and experimental contrast suggest that the ER-fMRI amplitude is greater than that predicted by a linear shift-invariant system.