Purpose. We have previously shown that an experimental, low-zinc environment decreased catalase activity in cultured human fetal retinal pigment epithelial (RPE) cells. The purpose of this study was to investigate the effect of zinc supplementation on catalase expression in cultured human fetal RPE cells. Methods. Confluent fetal RPE cells incubated in Goon's modified Ham's F12 (CMF-12) were treated (18 h) with zinc chloride (ZnCl2) (15, 30, or 100 mu M) to assess changes in catalase enzyme activity or for 6 h to assess the induction of catalase mRNA by Northern analysis and in situ hybridization. RPE cells were also treated with 30 mu M ZnCl2 for 2, 6, 24, 48 and 72 h to assess the time course of changes in catalase enzyme activity, changes in mRNA levels and status of the Spl transcription factor. Results. Catalase activity was increased above control by the addition of 15, 30 and 100 mu M ZnCl2. Catalase gene expression was induced by 30 mu M zinc in 6 h, but decreased to nontreated control levels by 24 h. The transcription factor Spl was also activated by zinc treatment (30 mu M) which peaked at 2 h and declined to non-treated control levels by 24 h. Catalase enzyme activity peaked at 24 h and decreased to control levels by 72 h. Conclusions. Our results demonstrate that zinc treatment of RPE cells increases catalase expression and activates the transcription factor Spl. The results suggest zinc may play a role in the transcriptional regulation of catalase in RPE cells.