Recent animal studies have shown that the synapses between inner hair cells and the dendrites of the spiral ganglion cells they innervate are the elements in the cochlea most vulnerable to excessive noise exposure. Particularly in rodents, several studies have concluded that exposure to high level octave-band noise for 2 h leads to an irreversible loss of around 50% of synaptic ribbons, leaving audiometric hearing thresholds unaltered. Cochlear synaptopathy following noise exposure is hypothesized to degrade the neural encoding of sounds at the subcortical level, which would help explain certain listening-in-noise difficulties reported by some subjects with otherwise 'normal' hearing. In response to this peripheral damage, increased gain of central stages of the auditory system has been observed across several species of mammals, particularly in association with tinnitus. The auditory brainstem response (ABR) wave I amplitude and waves I-V amplitude ratio have been suggested as non-invasive indicators of cochlear synaptopathy and central gain activation respectively, but the evidence for these hearing disorders in humans is inconclusive. In this study, we evaluated the influence of lifetime noise exposure (LNE) on the human ABR and on speech-in-noise intelligibility performance in a large cohort of adults aged 29 to 55. Despite large inter-subject variability, results showed a moderate, but statistically significant, negative correlation between the ABR wave I amplitude and LNE, consistent with cochlear synaptopathy. The results also showed (a) that central gain mechanisms observed in animal studies might also occur in humans, in which higher stages of the auditory pathway appear to compensate for reduced input from the cochlea; (b) that tinnitus was associated with activation of central gain mechanisms; (c) that relevant cognitive and subcortical factors influence speech-in-noise intelligibility, in particular, longer ABR waves I-V interpeak latencies were associated with poorer performance in understanding speech in noise when central gain mechanisms were active; and (d) absence of a significant relationship between LNE and tinnitus, central gain activation or speech-in-noise performance. Although this study supports the possible existence of cochlear synaptopathy in humans, the great degree of variability, the lack of uniformity in central gain activation and the significant involvement of attention in speech-in-noise performance suggests that noise-induced cochlear synaptopathy is, at most, one of several factors that play a role in humans' speech-in-noise performance.