A mathematical model is derived from physiological considerations for slow potential waves (called spreading depression) in cortical neuronal structures. The variables taken into account are the intra- and extracellular concentrations of Na+, Cl-, K+, and Ca++, together with excitatory and inhibitor transmitter substances. The general model includes conductance changes for these various ions, which may occur at nonsynaptic and synaptic membrane together with active transport mechanisms (pumps). A detailed consideration of only the conductance changes due to transmitter release leads to a system of nonlinear diffusion equations coupled with a system or ordinary differential equations. We obtain numerical solutions of a set of simplified model equations involving only K+ and Ca++ concentrations. The solutions agree qualitatively with experimentally obtained time-courses of these two ionic concentrations during spreading depression. The numerical solutions exhibit the observed phenomena of solitary waves and annihilation of colliding waves.