We determined the effect of preseasonal intranasal short ragweed (SRW) immunotherapy in a double-blind, nonpaired, 20-wk study involving 33 SRW-sensitive patients. Patients were selected on the basis of an elevated IGE serum antibody level, a positive intradermal skin test, and a positive intranasal challenge to SRW antigen. SRW-treated patients sprayed SRW solutions intranasally six times a day for 12 wk preseasonally. Placebo-treated patients used nebulized solutions containing buffer or histamine that were interchanged randomly throughout this period. The SRW-treated group reported more preseasonal symptoms than the placebo-treated group (p less than 0.003); however, during the SRW pollination season, the SRW-treated group reported significantly less sneezing, nasal congestion, rhinorrhea, red/itchy eyes, itchy nose/throat, and cough/wheeze. Supplemental antihistamine usage was similar in both groups. The treatment did not affect serum IgE antibody levels to crude SRW, AgE Ra3, or Ra5 in either group at any time during the study. No significant production of IgG antibody to SRW was seen in either group. One SRW-treated patient developed acute sinusitis after 2 wk of treatment; otherwise no side effects other than symptoms of hay fever were noted. Although intranasal SRW immunotherapy may offer an effective and less costly alternative to parenteral immunotherapy, reduction in hay fever symptoms during the pollination season was achieved at the expense of provoking these symptoms during the preceding weeks.