['To evaluate whether the protective effect of melatonin on H2O2-induced caspase activation and DNA fragmentation depends on the interaction between melatonin and its surface receptors.', 'Laboratory study.', 'Center for assisted human reproduction at a Spanish hospital.', 'Twenty-one healthy donors.', 'Human spermatozoa were treated with increasing concentrations of hydrogen peroxide (H2O2; 1 μM, 10 μM, 100 μM, 1 mM) and preincubated with 1 mM melatonin.', 'Activation of caspase-3 and -9 as well as DNA fragmentation were examined by fluorescence methods.', 'Our findings showed that H2O2 induced a significant increase in caspase-9 and caspase-3, which was dose independent. Conversely, pretreatment with melatonin reduced H2O2-mediated caspase activation in a dose-dependent way. Moreover, the antiapoptotic effects of melatonin in ejaculated human spermatozoa may involve membrane melatonin receptor MT1. In addition, we found that the survival-promoting pathway extracellular signal-regulated kinase (ERK) is likely to have a role in the protective actions of melatonin in ejaculated human spermatozoa. Finally, we confirmed these results further by demonstrating that melatonin prevention of H2O2-induced DNA fragmentation is dependent on both MT1 receptor and ERK signaling.'] Does melatonin protect human spermatozoa from apoptosis via melatonin receptor- and extracellular signal-regulated kinase-mediated pathways?