Mating pheromone is the best-known fungal paracrine signal whose essentiality in determining sexual reproduction has been recognized since six decades ago. We demonstrate that the pheromone cannot induce mating response during unisexual mating due to the lack of a compatible receptor from the same unisexual population. We identify a quorum sensing (QS) peptide Qsp1 in place of pheromone as a specific intercellular signal directing Cryptococcus unisexual reproduction. A typical zinc finger regulator Cqs2 as the master regulator of QS signaling induces unisexual reproduction in response to Qsp1. Collectively, these data demonstrate that QS activation rather than pheromone induction as the pivotal social control mechanism underlies unisexual reproduction in C .neoformans. Overall design: 64 samples contain wild type, cqs1delta ,opt1delta and cqs2delta, expression profiles of wild-type (WT) and the cqs1delta mutant in the presence of glucose or galactose of two replicates.