Multiple sclerosis can produce highly selective losses in visual function. Psychophysical studies have demonstrated contrast sensitivity deficits for spatial frequencies or for stimulus orientations. Using real-time lock-in retrieval of the visual evoked potential, the authors measured contrast sensitivity in 15 cases with probable or definite multiple sclerosis and acuities of 20/40 or better. Sine-wave grating contrast threshold determinations for three spatial frequencies (1, 4, and 8 cycles/deg) and four orientations (0, 45, 90, and 135 deg) revealed contrast deficits in at least one spatial frequency and orientation in every case. In most cases the visual losses were spotty or multifocal, and not the same in both eyes. Some cases with highly selective patterns of orientation or spatial frequency losses were observed and are discussed in terms of involvement of cortical functional architecture in the disease.