The directly activated substrates for self-stimulation of the lateral hypothalamus (LH) and medial prefrontal cortex (MPFC) were described by comparing their strength-duration characteristics. The current required to maintain a half-maximal rate of lever pressing was traded off against the pulse duration while all other stimulation parameters were kept constant. In this manner, cathodal strength-duration curves were obtained at four LH and eight MPFC sites; anodal curves were obtained at two of the LH and six of the MPFC sites. In general, the cathodal LH curves had lower rheobases than the cathodal MPFC curves and continued to descend after the MPFC curves had levelled off. At short pulse durations, the anodal curves lay above the cathodal curves, a finding more pronounced in the LH data. The two sets of curves converged at the longer pulse durations. The differences in the strength-duration curves are consistent with the notion that different directly stimulated neurons are responsible for the rewarding effects of LH and MPFC stimulation. Anatomical and physiological properties that could account for these differences are discussed.