Fundamental frequency differences (ΔF0) between competing talkers aid in the perceptual segregation of the talkers (ΔF0 benefit), but the underlying mechanisms remain incompletely understood. A model of ΔF0 benefit based on harmonic cancellation proposes that a masker's periodicity can be used to cancel (i.e., filter out) its neural representation. Earlier work suggested that an octave ΔF0 provided little benefit, an effect predicted by harmonic cancellation due to the shared periodicity of masker and target. Alternatively, this effect can be explained by spectral overlap between the harmonic components of the target and masker. To assess these competing explanations, speech intelligibility of a monotonized target talker, masked by a speech-shaped harmonic complex tone, was measured as a function of ΔF0, masker spectrum (all harmonics or odd harmonics only), and masker temporal envelope (amplitude modulated or unmodulated). Removal of the masker's even harmonics when the target was one octave above the masker improved speech reception thresholds by about 5 dB. Because this manipulation eliminated spectral overlap between target and masker components but preserved shared periodicity, the finding is consistent with the explanation for the lack of ΔF0 benefit at the octave based on spectral overlap, but not with the explanation based on harmonic cancellation.