Either isolated normal or preswollen rabbit corneas were perfused across their endothelial surface with various drugs in the specular microscope. The deswelling rate of preswollen corneas was uninfluenced by calmodulin (1 and 10μg/ml), phenylephrine (0.1 and 1 mM), DbcAMP (10–4M), theophylline (10–3and 10–4M), isoproterenol (2×10–7and 2×10–6M), or cyclic GMP (10–4and 10–6M). The swelling rate of normal thickness corneas was increased by furosemide (10–5and 10–4M) and thiocyanate (5×10–2and 5×10–3M) but not by SITS (10–3M), dipyridamole (5×10–5M) or NAP-taurine (10–3M). The results suggest that alteration of endothelial cyclic AMP or cyclic GMP levels has no influence on transendothelial fluid flow. Modulation of the metabolic processes underlying anion fluxes by furosemide and thiocyanate caused corneal swelling but none of the agents which affect passive anion exchange in other systems influenced transendothelial fluid movement. The furosemide and thiocyanate effects confirm that bicarbonate, or chloride, exchange may be important in part in the regulation of corneal dehydration by the endothelium.