This study investigated the cellular response of human lymphocytes to Dermatophagoides pteronyssinus crude antigen and 14 molecular weight (MW) fractions. The cells were derived from atopic patients and healthy individuals who were skin test-positive or skin test-negative to mite antigen. When stimulated with crude antigen, the group of patients showed elevated proliferation and production of lymphokine in comparison with the healthy skin test-negative individuals (P less than 0.01). By stimulation with fractions, there was a remarkable variety in the responding patterns to each fraction. However, when expressed as a mean value, the patient group exhibited a sharp and high peak at 95,000 MW, which is different from IgE responses. In the other two groups, no apparent peak response was observed. Lymphokine production by fraction stimulation was studied in six distinct individuals. The most important fractions for inducing lymphokine production differed in each individual tested. Moreover, fractions which induced active lymphokine production were not necessarily the main targets of proliferative response in atopic patients.