Human airway epithelial cells (AEC) produce the T cell growth factor interleukin (IL)-2 that likely modulates the T cell lung inflammatory response. IL-2 mRNA from cultured AEC and from Jurkat T cells was analyzed by reverse transcription-polymerase chain reaction and Northern hybridization. IL-2 mRNA is present constitutively in AEC and is enhanced twofold after stimulation with phorbol 12-myristate 13-acetate (PMA; 20 ng/ml) + histamine (2 mM). Normal human AEC secrete IL-2 at rest (7 pg/ml), and IL-2 secretion is increased threefold after stimulation with PMA + histamine; this increase is inhibited by dexamethasone and diphenhydramine. Transcriptional regulation of IL-2 was investigated with a transgenic human AEC line, 16HBE/IL-2 luciferase; there is constitutive IL-2 transcription at rest, and IL-2 transcription is enhanced 8-fold by PMA and 25-fold by PMA + histamine. IL-2 regulation differs fundamentally between AEC and Jurkat T cells. AEC IL-2 likely promotes local proliferation of T cells and may contribute to pathological airway inflammation in asthma.