Mammalian parents participate in infant care. We previously demonstrated that sires of a strain of non-monogamous laboratory mice initiate parental retrieval behavior in response to olfactory and auditory signals from the dam during isolation in a new environment. This behavior is rapidly lost in the absence of such signals when the sires are caged alone. The neurocircuit and hormones that control such paternal behavior are not wellunderstood. CD38, a membrane glycoprotein, catalyzes synthesis of cyclic ADP-ribose and facilitates oxytocin (OT) secretion in oxytocinergic neurons in the hypothalamus, because formed cyclic ADP-ribose increases in cytosolic free calcium concentrations. Here, we studied CD38 in the nucleus accumbens (NAcc) on paternal pup retrieval behavior using CD38 knockout (CD38–/–) mice of the ICR strain. CD38–/– sires failed to retrieve when they were reunited with their pups after isolation together with the mate dams, but not with pup, in a novel cage for 10 min. When human CD38 was introduced in the NAcc of CD38–/– sires using a lentiviral infection technique, the sires expressing CD38 in the NAcc showed retrieval behavior. Complete recovery of retrieval was obtained in sires with the expression of CD38 in the NAcc in combination with OT administration.