Amitriptyline and chlordiazepoxide in bulk and formulation were estimated by stability indicating reverse phase high performance liquid chromatographic method. For the proposed method the chromatographic conditions are C18 column (250mm×4.6mm i.d., 5µ particle size), mobile phase was mixture of acetonitrile and triethylamine buffer pH 2.5 at a ratio of 30:70. The injection volume was 20µl with a flow rate 1.0ml/min at a ambient temperature. The wave length selected was 220nm and retention times were found to be 4.55 and 5.893mins for amitriptyline and chlordiazepoxide respectively. Amitriptyline shows linear curve at a concentration range of 5-20µg/ml and for chlordiazepoxide the linearity was obtained for the concentration range of 1.8-6.4µg/ml and regression coefficient was found to be 0.997 and 0.999 for amitriptyline and chlordiazepoxide. The limit of detection  and limit of quantification for amitriptyline was found to be 0.02µg/ml and 0.05µg/ml and for chlordiazepoxide was found to be 0.01µg/ml and 0.03µg/m. amitriptyline and chlordiazepoxide shows recoveries were ranged  from 99.98% – 100.08 % and 99.96%- 100%respectively. The method was performed based on ICH guidelines. In the detection of these drugs degradation products were not interfered and the method was considered as new stability indicating method.