Although the antigenic composition of short ragweed pollen has been extensively investigated, very few studies have analyzed the allergenic cross-reactivity among various types of ragweed pollens. Using a serum pool from patients sensitive to short ragweed, we studied the cross-reactivity of IgE antibodies to six ragweeds by the radioallergosorbent test. Extracts were analyzed for their inhibitory activities with solid-phase allergens prepared from all of the ragweed pollens. Also, samples of serum were absorbed with the various solid-phase allergens and the reactivity of the remaining IgE antibodies was determined. Two patterns of reactivity were observed. Short, giant, western, and false ragweeds displayed comparable reactivity in both inhibition and absorption experiments. Slender and southern ragweed were considerably less active, indicating that they lacked allergenic groupings possessed by the other species. These same patterns of cross-reactivity were found using ragweed pollens from four commercial sources. Knowledge of these patterns of cross-allergenicity is of importance for diagnosis and treatment of sensitive patients as well as for in vitro standardization of extracts.