In a fed and orally stimulated state, whether the addition of monosodium glutamate (MSG) (alone or in combination with inosine monophosphate-5 (IMP-5)) to a high-protein (HP) meal leads to early satiety and a difference in energy intake at a second course was investigated. Ten men and twelve women consumed, in random order, a first-course meal consisting of: (1) water (control); (2) a HP meal with 0.6% MSG and 0.25% IMP-5; (3) a HP meal with no additives; (4) a HP meal with MSG only; (5) a sham-fed meal 2 (oral-stimulation). Appetite perceptions, plasma concentrations of glucagon-like peptide 1 (GLP-1), glucose and insulin, and energy intake at a buffet (i.e. a second course) were measured before and after each condition. Changes in appetite, and in GLP-1, glucose and insulin, were similar for the three fed HP conditions and all were greater (post hoc all P < 0.01) than the control and sham conditions. Energy intake was not different following the HP+MSG+IMP (1.86 (SEM 0.3) MJ) as compared with the HP+MSG-only (2.24 (SEM 0.28) MJ) condition (P = 0.08), or for the HP+MSG+IMP compared with the HP no-additives condition (1.60 (SEM 0.29) MJ) (P = 0.21). Following the HP+MSG-only condition, 0.64 (SEM 0.20) MJ more energy was consumed compared with the HP no-additives condition (P = 0.005). We conclude that the addition of MSG to a HP meal does not influence perceptions of satiety and it may increase energy intake at a second course. Cephalic responses after the sham condition were of similar magnitude to the control and therefore just tasting food is not enough to influence appetite and energy intake.