Pentigetide is a polar peptide derived from Immunoglobulin E (IgE) Fc region, with two acidic side chains, a basic side chain and free termini. It was developed to inhibit IgE-mediated allergic responses. A randomized, double-blind, placebo-controlled trial was conducted to evaluate the safety and efficacy of subcutaneously administered pentigetide in the treatment of allergic rhinitis. Mean symptom scores indicated that the frequency and severity of sneezing, rhinorrhea, and nasal itching decreased after 1 week of pentigetide treatment and remained decreased until study completion, whereas congestion was unchanged or slightly increased. In contrast, the frequency and severity of sneezing, rhinorrhea, and nasal itching increased after placebo treatment, with congestion essentially unchanged. No clinical or statistical differences in safety parameters between pentigetide and placebo treatments were observed. This double-blind, active-controlled trial demonstrates that pentigetide, 0.5%, ophthalmic solution is safe and effective in the treatment of allergic conjunctivitis. Pentigetide nasal solution was safe and effective for the treatment of seasonal allergic rhinitis.