AbstractEnvelope (E) and temporal fine structure (TFS) are important features of acoustic signals and their corresponding perceptual function has been investigated with various listening tasks. To further understand the underlying neural processing of TFS, experiments in humans and animals were conducted to demonstrate the effects of modifying the TFS in natural speech sentences on both speech recognition and neural coding. The TFS of natural speech sentences was modified by distorting the phase and maintaining the magnitude. Speech intelligibility was then tested for normal-hearing listeners using the intact and reconstructed sentences presented in quiet and against background noise. Sentences with modified TFS were then used to evoke neural activity in auditory neurons of the inferior colliculus in guinea pigs. Our study demonstrated that speech intelligibility in humans relied on the periodic cues of speech TFS in both quiet and noisy listening conditions. Furthermore, recordings of neural activity from the guinea pig inferior colliculus have shown that individual auditory neurons exhibit phase locking patterns to the periodic cues of speech TFS that disappear when reconstructed sounds do not show periodic patterns anymore. Thus, the periodic cues of TFS are essential for speech intelligibility and are encoded in auditory neurons by phase locking.