Purpose This pilot phase I trial evaluated the safety and maximum-tolerated dose of p53 gene transfer using an adenovirus vector (Ad-p53) delivered via bronchoalveolar lavage (BAL) to patients with bronchioloalveolar lung carcinoma (BAC). Patients and Methods Patients were initially administered two treatments of Ad-p53 to a single involved lobe, beginning at 2 × 109 viral particles (vp) per dose and escalated to a maximum of 2 × 1012 vp. If a clinical benefit was seen and the treatment was well tolerated, additional doses could be administered to additional lobes. Results Twenty-five patients were treated at doses between 2 × 109 and 2 × 1012 vp. At 2 × 1012 vp, one patient experienced grade 4 pulmonary toxicity, and one patient died 25 days after his second cycle; therefore, a cohort of 10 patients was treated at the recommended phase II dose of 5 × 1011 vp, with no grade 4 toxicity observed. The most frequent toxicities included low-grade fever, hypoxia, and dyspnea. Of the 23 assessable patients, 16 had stable disease as their best response. Subjective improvement in breathing was noted in eight patients. Limited distribution of vector was observed, with transient detection in patient sputum for 1 to 2 days after administration. Conclusion Ad-p53 can be administered safely by BAL at 5 × 1011 vp with repeated dosing. Stabilization of disease and symptomatic improvement may warrant further studies of Ad-p53 or other adenoviruses administered by BAL in patients with BAC.