Prolonged head elevation is thought to be a major contributor to the increased risk of respiratory disease associated with transportation in horses. Prior investigations have focused on immunological changes in the lower respiratory tract. The aim of this study was to characterize the response to head elevation in the upper respiratory tract. Twelve horses (mean ± SEM, 552 ± 10 kg; 11.5 ± 1.4 y) were tethered for 12 h with their heads elevated at a height of 1.5 m to induce physiological stress. While tied, horses had unlimited access to bermudagrass hay and were offered water every 2 h. Each horse underwent head elevation on 4 occasions, each separated by 30 d. When not tied, horses were maintained on pasture forage. Nasopharyngeal flush (NPF) and saliva samples were obtained before head elevation, immediately after (0 h), and 12, 24, and 72 h post head elevation. Mucus content and leukocyte populations were quantified in NPF and IgA was measured in saliva. Data were compared using mixed model ANOVA with repeated measures. NPF samples contained more mucus at 0 h post (P < 0.02) compared with pre-head tie samples. Percentage and number of neutrophils in NPF increased at 0 h post (P < 0.0001) and the number remained elevated through 72 h (P = 0.04). Lymphocytes, monocytes, and eosinophils in NPF increased in number (P < 0.05) but decreased in percent (P < 0.05) in response to head elevation. While the proportion of these cells normalized by 72 h, the numbers declined to levels lower than pre-head tie values. Percentage of CD8+ T cells and B cells in NPF were lower at 0 h post (P < 0.05) and returned to baseline by 12 h. Percentage of CD4+ and the ratio of CD4+ to CD8+ cells increased at 0 h post (P < 0.01) and remained elevated through 72 h (P < 0.05). Salivary IgA increased at 0 h post (P < 0.0001), then decreased below baseline at 12 h post (P < 0.0001) and remained lower than pre-head elevation values through 72 h (P < 0.05). The immunological changes observed in the upper respiratory tract agree with those reported for lower tract, and highlight increased risk of disease following prolonged head elevation.