Few or no S-100 determinants are detectable in normal human retina. However, the expression of this antigen was observed on the retinal Muller cells of eyes with sympathetic ophthalmia or uveitis. This finding, along with other experimental data, may be interpreted as indicating the retinal Muller cells may have an immunoactive role. Although the possibility of non-specific expression of the S-100 antigen during intraocular inflammation cannot be ruled out, it is postulated that, in the retina, Muller cells may have immunomodulating role similar to that of other S-100-positive/Ia-positive cells of certain lymphoid tissues.