A simple, selective, precise and stability-indicating high-performance thin-layer chromatographic method of analysis of imatinib mesylate both as a bulk drug and in formulations was developed and validated. The method employed HPTLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of chloroform:methanol (6:4, v/v). The system was found to give compact spot for imatinib mesylate (Rf value of 0.53 ± 0.02). Densitometric analysis of imatinib mesylate was carried out in the absorbance mode at 276 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r2 = 0.9966 ± 0.0013 with respect to peak area in the concentration range 100-1000 ng per spot. The mean value ± S.D. of slope and intercept were 164.85 ± 0.72 and 1168.3 ± 8.26 with respect to peak area. The method was validated for precision, recovery and robustness. The limits of detection and quantitation were 10 and 30 ng per spot, respectively. Imatinib mesylate was subjected to acid and alkali hydrolysis, oxidation and thermal degradation. The drug undergoes degradation under acidic, basic, oxidation and heat conditions. This indicates that the drug is susceptible to acid, base hydrolysis, oxidation and heat. Statistical analysis proves that the method is repeatable, selective and accurate for the estimation of said drug. The proposed developed HPTLC method can be applied for identification and quantitative determination of imatinib mesylate in bulk drug and dosage forms. © 2006 Elsevier B.V. All rights reserved.