We analyze the relation between the short-distance behavior of quantum field theory and the strong-field limit of the background field formalism, for QED effective Lagrangians in self-dual backgrounds, at both one and two loop. The self-duality of the background leads to zero modes in the case of spinor QED, and these zero modes must be taken into account before comparing the perturbative β function coefficients and the coefficients of the strong-field limit of the effective Lagrangian. At one-loop this is familiar from instanton physics, but we find that at two-loop the role of the zero modes, and the interplay between IR and UV effects in the renormalization, is quite different. Our analysis is motivated in part by the remarkable simplicity of the two-loop QED effective Lagrangians for a self-dual constant background, and we also present here a new independent derivation of these two-loop results.