Interactions between size and orientation-specific mechanisms in the human visual system were investigated using a sequential adaptation technique. Subjects adapted to a vertical, 4c/deg high-contrast (0.7) sinewave grating that was interleaved at a rate of 0.5 Hz with another adapting grating differing either in (1) spatial frequency or (2) orientation. Before and after adaptation contrast thresholds were measured for a vertical 4c/deg sinewave test grating. The resultant elevation in contrast threshold was plotted as a function of the (1) spatial frequency or (2) orientation differences between the first and second adapting gratings. Maximum threshold elevation was found when both adapting gratings shared the same spatial frequency and orientation. Minimum elevations were found when the second grating's spatial frequency or orientation differed by approx. 1.5 octaves or 45 deg, respectively. Beyond these values threshold elevations reapproached the baseline value measured in a control condition, where the 4.0 c/deg adapting grating was interleaved with a blank. The minimum threshold elevations were 0.2–0.3 log units below the baseline level. The results suggest the existence of inhibitory interactions between neural mechanisms tuned to the size and orientation of retinal images.