Bronchioloalveolar carcinoma (BAC), a form of pulmonary adenocarcinoma, presents unique clinical features, such as endobronchial spread and bronchorrhea in advanced stages. The prognosis for BAC patients in advanced stages is poor, as is the case for patients with other non-small-cell lung cancer (NSCLC) types, because of low susceptibility to conventional chemotherapy. Recently, an orally active, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI), ZD1839 ("Iressa"), has been investigated in phase II clinical studies (IDEAL 1 and IDEAL 2) as monotherapy against chemotherapy-refractory NSCLC, and provided clinically significant antitumor activity. In this study, we examined the therapeutic efficiency of ZD1839 in chemotherapy-refractory BAC patients with bronchorrhea. Two female BAC patients with bronchorrhea were treated once daily with ZD1839 (250 mg/day). In both cases, serous sputum production was dramatically reduced within 3 days of starting the treatment, and hypoxia and radiographic signs of bilateral lung consolidation were visibly improved within 7 days. Following more than 8 months of treatment, no evidence of recurrence or severe adverse events has been observed. These results suggest that this selective EGFR-TKI, ZD1839, may be a powerful agent for treatment of chemotherapy-refractory BAC patients with bronchorrhea.