To understand the relevance of allergens in generation of C3a, C4a, and C5a in normal human serum, we studied extracts of several allergens (house dust, house dust mite, Aspergillus fumigatus, and perennial ryegrass). Known complement activators zymosan and endotoxin were used as controls. Generation of C3a, C4a, and C5a (determined by radioimmunoassays) occurred with extracts of house dust and Aspergillus more than with house dust mite and ryegrass. Anaphylatoxins were produced both in dose and time-dependent fashions. Serum activated with house dust and Aspergillus extracts induced neutrophil aggregation when this serum was added to neutrophil suspensions. Less aggregation occurred when house dust mite and perennial ryegrass extract-activated sera were added to human neutrophils. We propose that some allergens may induce biologic responses by activation of sera and generation of anaphylatoxins as well as by IgE-mediated responses.