Background: The mechanism of T(H)2/T(H)17-predominant and T(H)2/T(H)17-low asthma is unknown. Objective: We sought to study the immune mechanism of T(H)2/T(H)17-predominant and T(H)2/T(H)17-low asthma. Methods: In a previously reported cohort of 60 asthmatic patients, 16 patients were immunophenotyped withT(H)2/T(H)17-predominant asthma and 22 patients with T(H)2/T(H)17-low asthma. We examined bronchoalveolar lavage (BAL) fluid leukocytes, cytokines, mediators, and epithelial cell function for these asthma subgroups. Results: Patients with T(H)2/T(H)17-predominant asthma had increased IL-1 beta, IL-6, IL-23, C3a, and serum amyloid A levels in BAL fluid, and these correlated with IL-1 beta and C3a levels. T(H)2/T(H)17 cells expressed higher levels of the IL-1 receptor and phospho-p38 mitogen-activated protein kinase. Anakinra, an IL-1 receptor antagonist protein, inhibited BALT(H)2/T(H)17 cell counts. T(H)2/T(H)17-low asthma had 2 distinct subgroups: neutrophilic asthma (45%) and pauci-inflammatory asthma (55%). This contrasted with patients with T(H)2/T(H)17-predominant and T(H)2-predominant asthma, which included neutrophilic asthma in 6% and 0% of patients, respectively. BAL fluid neutrophils strongly correlated with BAL fluid myeloperoxidase, IL-8, IL-1a, IL-6, granulocyte colony-stimulating factor, and GM-CSF levels. Sixty percent of the patients with neutrophilic asthma had a pathogenic microorganism in BAL culture, which suggested a subclinical infection. Conclusion: We uncovered a critical role for the IL-1 beta pathway in patients with T(H)2/T(H)17-predminant asthma. A subgroup of patients with T(H)2/T(H)17-low asthma had neutrophilic asthma and increased BAL fluid IL-1 alpha, IL-6, IL-8, granulocyte colony-stimulating factor, and GM-CSF levels. IL-1 alpha was directly involved in IL-8 production and likely contributed to neutrophilic asthma. Sixty percent of neutrophilic patients had a subclinical infection.