We recently reported neurotrophin-4 (NT-4) knockout mice lacking 90% of vagal afferents innervating the smooth muscle of the small intestine (intraganglionic laminar endings, IGLEs) and this loss is associated with deficits in short-term satiety (intake associated with a single meal), whereas long-term feeding controls (intake integrated across several meals) appeared intact (Fox et al., J.Neurosci,21,8602,2001). However, since nutritionally balanced diets were used in this study, it is possible that the missing vagal afferents might play a role in long-term regulation under more challenging conditions. To examine this, we subjected NT-4 mutants and wild types to a diet regime of intermittent hi-fat exposure that produces dramatic hyperphagia relative to continuous hi-fat exposure (Byerly & Fox, 2001 SFN mtg). NT-4 mutants and wild types (n=26) received either (1) continuous access to a 43% fat source ad libitum or (2) alternating access to the 43% fat source on even-numbered days and powdered chow on odd-...