The mixed dissociation constants of two drugs-butorphanol and zolpidem-at temperatures of (25 and 37) degrees C were determined with the use of multiwavelength and multivariate treatments of spectral data using SPECFIT/32 and SQUAD(84) nonlinear regression. The factor analysis in the INDICES program predicts the correct number of components, that is, the number of dissociated and nondissociated forms of the molecules studied. The thermodynamic dissociation constant pK(a)(T) was estimated by nonlinear regression of {pK(a), I} data at (25 and 37) degrees C: for butorphanol pK(a,1)(T) = 9.46(1) and 8.99(3) and pK(a,2)(T) = 9.64(2) and 9.34(3); for zolpidem pK(a,1)(T)= 6.33(3) and 6.14(1), where the standard deviation in last significant digits is in parentheses. The proposed procedure involves chemical model building, calculating the concentration profiles, and fitting the protonation constants of the chemical model to multiwavelength and multivariate data measured. If the proposed protonation model represents the data adequately, the residuals should form a random pattern with a normal distribution N(0, s(2)), with the residual mean equal to zero, and the standard deviation of residuals being near to experimental noise. PALLAS and MARVIN predict pK(a) based on the structural formulas of drug compounds in agreement with the experimental value.