Our aim was to characterize and quantitate changes in two key neuropeptides, substance P (SP) and vasoactive intestinal peptide (VIP), that are involved in governing neurally-mediated gastrointestinal (GI) reflex activity during enteric inflammation in the ferret. Neuropeptide content was determined by radioimmunoassay of extracts of jejunal, ileal and colonic muscularis externa from uninfected ferrets and ferrets infected with enteric stages of the parasitic nematode, Trichinella spiralis. Increased myeloperoxidase activity (MPO), an enzymatic marker of inflammation, occurred in all three gut regions. Histopathological changes were present only in the small intestine. Significant reductions were detected in both SP (72% decrease) and VIP (62% decrease) in the inflamed jejunum. Ileal concentrations of both SP (77% decrease) and VIP (46% decrease) were also decreased during T. spiralis infection compared to uninfected ferrets. Only SP (58% decrease) concentration showed a significant change in colonic tissues from infected ferrets; colonic VIP was unaltered. Parasite-induced inflammation caused significant changes in peptide-containing enteric neural pathways and might contribute to functional GI motor disturbances that occur during nematode infections in mammalian hosts.