A panel of 188 unrelated Caucasian subjects who were exposed to the larvae of Chironomus thummi (Diptera, nonbiting midges) was HLA-typed by polymerase chain reaction amplification of the second exons of the DRB, DQA1, and DQB1 genes followed by dot-blot hybridization with sequence-specific oligonucleotide probes. Type I sensitization to the allergen Chi t I and a large number of other inhalant allergens was determined by RAST and skin testing. Sixty-one individuals were found to be sensitized to Chi t I, of whom 24 were sensitive to this allergen and to no other allergens tested. Statistical analyses showed that only in the latter group were the HLA-D genes DRB1*0101, DQA1*0101, and DQB1*0501 associated with IgE-responsiveness to Chi t I. These results suggest that HLA associations with responsiveness to certain allergens may be more striking in monosensitized subjects.