Purpose. Experiments were designed to determine wether acetazolamide (carbonic anhydrase inhibitor) alters PGE 1 and PGE 2 -induced cAMP accumulation in cultured human retinal pigment epithelial (RPE) cells, an effect which would suggest alterations of hormone-receptor interaction and/or adenylate cyclase activation. It will further elucidate the mechanisms of acetazolamide in the treatment of cystoide macular edema, and propose a method of local therapeutic intervention.Methods. RPE cells in the fifth passage were incubated at 37 o C for 30 minutes in the presence of 1 mM IBMX (control) and with and without 3 x 10 - 6 to 10 - 4 M acetazolamide (5-acetamido 1, 3, 4-thiadiazole-2-sulfonamide) in combination with 10 - 7 to 10 - 5 M PGE 1 or PGE 2 . Intracellular cAMP was extracted and determined by radioimmunoassay.Results. Acetazolamide alone had no effect on human RPE cAMP levels. PGE 1 and PGE 2 were potent stimulators of adenylate cyclase in the absence of acetazolamide. However, these PGs had 50-80% lower effect on cAMP levels (p0,01) when cells were incubated in the presence of various concentrations of acetazolamide.Conclusions. The effect of acetazolamide on human RPE cAMP levels in the presence of PGE 1 and PGE 2 indicate that acetazolamide interferes with PG receptor binding. Moreover, our results show trat acetazolamide alone did not interfere with adenylate cyclase activation. This may provide a more specific and an alternative topic therapeutic intervention for cystoid macular edema in the future.