biostudies-literatureAgron SNIDCD NIH HHSNational Institute on Deafness and Other Communication DisordersIsrael Science FoundationRob and Cheryl McEwen Fund for Brain ResearchNational Institutes of HealthNational Science Foundatione3002442https://www.ebi.ac.uk/biostudies/studies/S-EPMC10734982biostudies-literatureUnknown21(12)Rodent tears contain social chemosignals with diverse effects, including blocking male aggression. Human tears also contain a chemosignal that lowers male testosterone, but its behavioral significance was unclear. Because reduced testosterone is associated with reduced aggression, we tested the hypothesis that human tears act like rodent tears to block male aggression. Using a standard behavioral paradigm, we found that sniffing emotional tears with no odor percept reduced human male aggression by 43.7%. To probe the peripheral brain substrates of this effect, we applied tears to 62 human olfactory receptors in vitro. We identified 4 receptors that responded in a dose-dependent manner to this stimulus. Finally, to probe the central brain substrates of this effect, we repeated the experimenPLoS biologyA chemical signal in human female tears lowers aggression in males.PMC10734982R01 DC016224DC014423K99 DC018333R01 DC014423K99DC0183331555919DC016224714103Weissgross Rde March CAMatsunami HGorodisky LSobel NMishor EWeiss TFurman-Haran EAgron SfalseA chemical signal in human female tears lowers aggression in males.Rodent tears contain social chemosignals with diverse effects, including blocking male aggression. Human tears also contain a chemosignal that lowers male testosterone, but its behavioral significance was unclear. Because reduced testosterone is associated with reduced aggression, we tested the hypothesis that human tears act like rodent tears to block male aggression. Using a standard behavioral paradigm, we found that sniffing emotional tears with no odor percept reduced human male aggression by 43.7%. To probe the peripheral brain substrates of this effect, we applied tears to 62 human olfactory receptors in vitro. We identified 4 receptors that responded in a dose-dependent manner to this stimulus. Finally, to probe the central brain substrates of this effect, we repeated the experimen2023-01-01T00:00:00Z2023 Dec2026-06-03T12:35:03.827Z2025-04-04T08:44:03.156ZS-EPMC107349823812783710.1371/journal.pbio.3002442