Fraction A, a concentrate derived from short ragweed extract by (NH4)2SO4 precipitation, contains all major allergens including antigen E. Therapeutic efficacy and safety of this alum-adsorbed product was evaluated in a multicenter double-blind clinical trial by comparing it to placebo in 131 randomly matched ragweed hay fever patients who were not treated for at least 1 year. Therapeutic response to fraction A injections was more significant than placebo (p <0.05) by investigators’ evaluation, by average daily symptom score (1.097 vs. 1.378, p <0.05) during the peak ragweed season, or by average proportion of days in which medication was required (0.411 vs. 0.584, p = 0.01). Fraction A patients exhibited a significantly higher (p <0.0005) increase in hemagglutinating titer after treatment than placebo controls. Radioallergosorbent binding, evaluated in a subgroup of 31 patients before and after the ragweed season, was unchanged or decreased in 12 of 15 patients treated with fraction A. In contrast, 9 of 16 placebo-treated patients showed an increase in this index. Systemic effects were noted after 42 (1.5%) of 2.641 injections, while local reactions occurred at the rate of 2.3%. It is concluded that a single course of preseasonal immunotherapy wih alum-adsorbed fraction A is effective and relatively safe.