The present work involves an investigation of the thermal and photochemical degradation of betamethasone esters i.e. betamethasone valerate and betamethasone dipropionate under various conditions and the evaluation of the photoxicity of these compounds. The thermal degradation (40oC) of betamethasone-17-valerate leads to the formation of betamethasone-21-valerate and betamethasone alcohol whereas betamethasone dipropionate gives rise to betamethasone-17-propionate, betamethasone-21-propionate and betamethasone alcohol at pH 2.5-7.5, betamethasone-21-propionate being an intermediate in this reaction. The betamethasone esters on photodegradation, using a UV radiation source (300-400nm), yield two major unknown products in aqueous and organic solvents. The detection of the photodegradation products of betamethasone valerate and betamethasone dipropionate has been carried out by HPLC and the tR values of the unknown products have been reported. The USP HPLC method, after proper validation, has been used for the assay of betamethasone esters and their thermal and photodegradation products. The analytical data have been used to evaluate the kinetics of thermal and photochemical reactions. In both reactions the betamethasone esters have been found to follow the first-order kinetics under the conditions employed. The apparent first-order rate constants for the thermal degradation of betamethasone valerate and betamethasone dipropionate in various media lie in the range of 0.339-9.07x10-3 hr-1 and 0.239-1.87x10-3 hr-1, respectively. The values of these rate constants for the photodegradation of betamethasone valerate and betamethasone dipropionate are in the range of 1.617-11.303x10-3 min-1 and 1.101- 7.657x10-3 min-1, respectively. The buffer and ionic strength effects on the rate of thermal and photodegradation have also been studied. It has been found that phosphate buffer inhibits the rate of degradation of both esters at pH 7.5. This could be due to deactivation of the thermal and photo-excited species involved in the reaction .An increase in the ionic strength of the phosphate buffer also leads to a decrease in the rate of reaction. Attempts on photostabilization of betamethasone esters in cream and gel formulations using compounds causing spectral overlay (vanillin and butyl hydroxytoluene) and light scattering agent (titanium dioxide) show promising results. However, the use of titanium dioxide was most effective in the photostabilization of the esters, causing 39.62-42.56 % and 33.84-35.70 % greater protection in cream and gel formulations compared to the control formulations of betamethasone valerate and betamethasone dipropionate, respectively. An important aspect of this work has been the evaluation of in vitro phototoxicity of betamethasone esters. This involved the application of the tests including photohemolysis, lipid photoperoxidation and protein photodamage. The results indicate that betamethasone esters and their photodegradation products are toxic to mouse red blood cells under UV irradiation. Photodegradation products of the esters are toxic in the dark also, therefore, appropriate precautions may be taken in their clinical applications to avoid any adverse effects.