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A carefully controlled study allowed us to compare the sensitivity of ASL (arterial spin labeling) and BOLD (blood oxygen level dependent) fMRI for detecting the effects of the adenosine A2a antagonist tozadenant in Parkinson disease . Only ASL detected the direct effect of tozadenant. BOLD was more sensitive to a cognitive task, which (unlike most drugs) allows on-off comparisons over short periods of time. Neither ASL nor BOLD could detect a cognitive-pharmacological interaction. These results are consistent with the known relative advantages of each fMRI method, and suggest that for drug development, directly imaging pharmacodynamic effects with ASL may have advantages over cognitive-pharmacological interaction BOLD, which has hitherto been the more common approach to pharmacological fMRI.