We present a comparison of x-ray diffraction methods for the determination of the critical layer thickness for dislocation multiplication in mismatched heteroepitaxy. The conventional x-ray diffraction method for determination of the critical layer thickness is based on the direct observation of the lattice relaxation in measurements of strain (the “strain method”). An indirect method is based on the observation of the x-ray rocking curve broadening by the threading dislocations, which are introduced concurrently with misfit dislocations (the “full width at half maximum (FWHM) method”). For this study, we have applied both methods to ZnSe grown on GaAs (001) by metalorganic vapor phase epitaxy (MOVPE). We have compared the resolution of the two x-ray diffraction methods both theoretically and experimentally for the case of 004 reflections using Cukα1 radiation. Theoretically, we have shown that in this case the FWHM method is 2.6 times more sensitive to relaxation than the strain method. This conclusion is supported by our experiments, in which we determined a critical layer thickness value of 140 nm by the FWHM method, compared to 210 nm as determined by the strain method.