Laboratory mice drink little sucrose solution upon initial exposure, but later develop a strong preference for sucrose over water that plateaus after a few days. Both the initial neophobia and later plateau of sucrose intake may involve central oxytocin (OT) signaling pathways. If so, then mice that lack the gene for OT (OT KO) should exhibit enhanced initial and sustained sucrose intake compared to wild type (WT) cohorts. To test this hypothesis, female OT KO and WT mice (11-13 mo old) were given a 2-bottle choice between 10% sucrose and water available ad libitum for 4 days. On the first day, sucrose intake was 20-fold greater in OT KO mice compared to WT cohorts. The avid sucrose consumption by OT KO mice increased further on day 2 and was sustained at significantly higher levels than intake by WT mice. Enhanced initial and sustained sucrose intake also was observed in 5-7 mo old male OT KO mice. The effect of genotype was observed over a range of sucrose concentrations and was maintained over at least 8 days of continual exposure. However, there was no effect of genotype on daily intake of sucrose-enriched powdered chow. These findings indicate that the genetic absence of OT in mice is associated with enhanced initial and sustained intake of sucrose solutions. Thus, central OT pathways may normally participate both in limiting initial intake of novel ingesta, and may also participate in limiting intake of sweet, highly palatable familiar ingesta.