We investigated the physiological mechanism of grapheme-color synesthesia using metacontrast masking. A metacontrast target is rendered invisible by a mask that is delayed by about 60 ms; the target and mask do not overlap in space or time. Little masking occurs, however, if the target and mask are simultaneous. This effect must be cortical, because it can be obtained dichoptically. To compare the data for synesthetes and controls, we developed a metacontrast design in which nonsynesthete controls showed weaker dichromatic masking (i.e., the target and mask were in different colors) than monochromatic masking. We accomplished this with an equiluminant target, mask, and background for each observer. If synesthetic color affected metacontrast, synesthetes should show monochromatic masking more similar to the weak dichromatic masking among controls, because synesthetes could add their synesthetic color to the monochromatic condition. The target-mask pairs used for each synesthete were graphemes that elicited strong synesthetic colors. We found stronger monochromatic than dichromatic U-shaped metacontrast for both synesthetes and controls, with optimal masking at an asynchrony of 66 ms. The difference in performance between the monochromatic and dichromatic conditions in the synesthetes indicates that synesthesia occurs at a later processing stage than does metacontrast masking.