The study authors hypothesized that intralymphatic immunotherapy induces a better, more rapid response than do other types of immunotherapy for treating canine atopic dermatitis. Alum-precipitated allergen extract was injected into the popliteal lymph nodes of 51 participants. Twenty-two dogs completed the study and were included in a per-protocol analysis of results; all 51 participants were included in a separate intention-to-treat analysis. Pruritus and quality-of-life scores improved significantly in the intention-to-treat analysis; however, Canine Atopic Dermatitis Extent and Severity Index (CADESI) scores showed significant improvement only in the per-protocol analysis. Given the limited adverse effects, evaluation of intralymphatic immunotherapy as a safe, feasible, long-lasting treatment for canine atopic dermatitis is warranted.