In order to determine if defects in regulation of immune responses play a role in the pathogenesis of croup, we studied 37 infants and children with either croup or upper respiratory illness alone due to parainfluenza virus (PV). PV-specific IgE responses were determined by an enzyme-linked immunosorbent assay, cell-mediated immune responses to PV antigen were studied byin vitrolymphocyte transformation assays, and suppressor cell function was determined by addition of histamine to lymphocyte transformation assays. In comparison to patients with upper respiratory illness alone, patients with croup had increased production of PV-specific IgE antibody, increased lymphoproliferative responses to PV antigen, and diminished histamine-induced suppression of lymphocyte transformation responses to PV. These results suggest that a defect in suppressor function exists among croup patients. Similar defects have been demonstrated in bronchiolitis and atopic diseases, providing an immunologic link between the three illnesses.