Specific immunotherapy is effective in grass pollen allergy with standardized extracts and formalinized allergoids, but systemic reactions are not uncommon. A high-molecular-weight (>85,000 daltons), formalinized allergoid was investigated in a double-blind, placebo-controlled study to assess its safety and efficacy. Twenty patients received a placebo and 39 the allergoid using a rather aggressive protocol. Five patients developed a mild and transient systemic reaction with high doses of allergoid and one had a more severe reaction requiring treatment. Nasal challenges performed with orchard grass pollen grains showed that the threshold number of grains eliciting nasal symptoms was significantly (p <0.01) greater in the treated group. This group had significantly (p <0.01) less nasal symptoms during the season and specific IgG levels were significantly (p <0.01) elevated. There was a significant (p <0.01) correlation between nasal challenges and nasal symptoms during the season but no correlation between IgG and symptoms. There was no dose-dependent effect of allergoids.