This study was designed to investigate the inhibitory effect of 5-fluorouracil (5-FU) and dexamethasone (DEX) on the proliferation of human retinal pigment epithelial (RPE) cells in vitro. The human RPE cells (R-50 cell line) were cultured and exposed to various concentrations of combined 5-FU (0, 250, 500, 1000, 2000 ng/ml) and DEX (0, 1, 10, 100, 200 micrograms/ml). The cells were incubated for 96 hr and the medium was changed every 48 hr to replenish the drug action. Cell viability was assessed using cell counting and trypan blue exclusion method. Tetrazolium salt, which can be metabolized by mitochondrial dehydrogenase to form a formazan dye, was used to assay cell proliferation. Treatment with 5-FU alone inhibited cell proliferation in a dose-dependent manner. The concentration of 5-FU that inhibited growth by 50% (IC50) was found to be 704.12 ng/ml. There was a bimodal effect of DEX on RPE cells--stimulation at low concentrations (1, 10 micrograms/ml) and inhibition at high concentrations (100, 200 micrograms/ml). When the two drugs were combined, there was additive inhibition in the concentration of 200 micrograms/ml of DEX. These results indicate that a combination of 5-FU and DEX is no more effective in the inhibition of human RPE cells, except in combination with high concentrations of DEX (> or = 200 micrograms/ml).