Centrally acting oxytocin (OT) inhibits feeding. Recent evidence suggests a link between OT and control of carbohydrate and saccharin intake, but it is unclear whether OT affects appetite for only carbohydrates, especially sweet ones, or sweet tastants irrespective of their carbohydrate content. Therefore, a blood-brain barrier penetrant OT receptor antagonist, L-368,899, was administered in mice and intake of liquid diets containing carbohydrates sucrose, glucose, fructose, polycose, or cornstarch (CS) or the noncarbohydrate, noncaloric sweetener saccharin was studied in episodic intake paradigms: one in which only one tastant was available and the other in which a choice between a carbohydrate (sucrose, glucose, or fructose) and saccharin was provided. We also used real-time PCR to examine hypothalamic Ot mRNA levels in mice provided short-term access to sucrose, CS, or saccharin. In the no-choice paradigm, L-368,899 increased the intake of all carbohydrates, whereas its effect on saccharin consumption showed only a trend. A 10 times lower dose (0.3mg/kg) stimulated intake of sucrose than other carbohydrates. In the choice test, a very low 0.1mg/kg dose of L-368,899 doubled the proportion of sucrose consumption relative to saccharin, but did not affect fructose or glucose preference. Ot gene expression increased after sucrose and CS, but not saccharin exposure compared with the controls; however, a higher level of significance was detected in the sucrose group. We conclude that OT inhibits appetite for carbohydrates. Sucrose consumption considerably enhances Ot gene expression and is particularly sensitive to OT receptor blockade, suggesting a special functional relationship between OT and sugar intake.