The retinal pigment epithelium (RPE) plays several important roles in the continual support and renewal of photoreceptor outer segments. In the present study, we have demonstrated that RPE cells contain a low molecular weight protein with a high capacity for zinc binding that is dependent on available sulfhydryl groups. This protein is inducible by a 24 hour incubation of cultured RPE in medium supplemented with zinc, cadmium, or dexamethasone. The induction of this protein is correlated with an increased capacity for zinc-65 uptake into cultured RPE. Analysis with a cDNA probe specific for the human metallothionein II gene corroborated the existence and induction of metallothionein gene products in RPE cells. Based on these properties, we have identified this protein as metallothionein. The induction of metallothionein likely has a critical influence on the zinc economy of the RPE.