A novel alternative for the simultaneous determination of compounds with similar structure is described, using the whole chemiluminescence-time profiles, acquired by the stopped-flow technique, in combination with mathematical treatments of multivariate calibration. The proposed method is based on the chemiluminescent oxidation of morphine and naloxone by their reaction with potassium permanganate in an acidic medium, using formaldehyde as co-factor. The whole chemiluminescence-time profiles, acquired using the stopped-flow technique in a continuous-flow system, allowed the use of the time-resolved chemiluminescence (CL) data in combination with multivariate calibration techniques, as partial least squares (PLS), for the quantitative determination of both opiate narcotics in binary mixtures. In order to achieve overcoat the additivity of the CL profiles and beside to obtain CL profiles for each drug the most separated as possible in the time, the optimum chemical conditions for the CL emission were investigated. The effect of common emission enhancers on the CL emission obtained in the oxidation reaction of these compounds in different acidic media was studied. The parameters selected were sulphuric acid 1.0 mol L(-1), permanganate 0.2 mmol L(-1) and formaldehyde 0.8 mol L(-1). A calibration set of standard samples was designed by combination of a factorial design, with three levels for each factor and a central composite design. Finally, with the aim of validating the chemometric proposed method, a prediction set of binary samples was prepared. Using the multivariate calibration method proposed, the analytes were determined in synthetic samples, obtaining recoveries of 97-109%.