The influence of temperature and relative air humidity on the stability of omeprazole (OME) in solid state was studied. Changes in the concentration were monitored by HPLC with UV detection. The method was validated; its selectivity, range of linearity, precision, limit of detection (LOD) and limit of quantification (LOQ) were established. The linearity was satisfactory (r = 0.9998) in the concentration range from 0.5 to 14.0 mg/mL for a LiChrospher 100 RP-18 column (5 microm particle size, 100 mm x 4 mm, Merck, Darmstadt, Germany) and the mobile phase of methanol : 100 mM ammonium acetate (60:40 v/v). Degradation was conducted in solid phase at increased temperature (313 K to 393 K) and in the air humidity varying from 25% to 90% RH. The kinetic and thermodynamic parameters of OME decomposition in solid phase were determined.