Mice lacking the melanocortin-5 receptor (MC5R) exhibit decreased sensitivity to the stimulatory effects of systemic melanocortin injections on aggressive behavior. Because the pheromone-producing preputial gland expresses the MC5R, we tested the hypothesis that decreases in preputial pheromones underlie the behavioral deficit. Here we show that MC5R deficiency decreases preputial and urine levels of the sex pheromones, alpha- and beta-farnesene, relative to wild-type mice. We also demonstrate that farnesenes potently stimulate aggression in mice. Moreover, farnesene-stimulated aggression is reduced in MC5R-deficient mice, relative to wild-type mice. Our results suggest that activation of the MC5R promotes aggression by increasing farnesene signaling.