The method of separation of variables in the Dirac equation proposed in an earlier work by one of the present authors [J. Math. Phys. 30, 2132 (1989) ] is developed for the complete set of interactions of the Dirac particle. The essence of the method consists of the separation of the first-order matrix differential operators that define the dependence of the Dirac bispinor on the related variables, but commutation of such operators with or between the operator of the equation is not assumed. This approach, which is perfectly justified in the presence of gravitational [Theor. Math. Phys. 70, 204 (1987) ] or vector fields [J. Math. Phys. 30, 2132 (1989) ], permits one to find all the possibilities of separation of variables in the Dirac equation in the case of the most general set of external fields. The complete set of interactions of the Dirac particle is determined by the symmetry group of equations, namely, viz. the SU(4) group. The interactions are scalar, vector, tensor, pseudovector and pseudoscalar. The analysis in this article is limited to Cartesian coordinates. The corresponding results for the general curvilinear coordinates will be presented in a future paper. © 1991 American Institute of Physics.