Eight patients with a thoracic malignancy inhaled single doses of 3-100 x 10(6) IU of human natural interferon (IFN)-beta via a dosimeter-equipped jet nebulizer. After inhalation IFN-beta was not detectable in any of the serum samples as measured using an antiviral bioassay. Except for a slight body temperature rise and an 18% decrease in peak expiratory flow rate observed in 1 patient the patients did not experience any major side effects. Inhaled natural IFN-beta in this study was tolerated better than inhaled IFN-alpha or IFN-gamma in our previous studies. IFN-beta might thus be a promising local treatment for pulmonary diseases. Further work is needed to investigate the concentrations of biologically active IFN in alveolar epithelial lining fluid after inhalation and the therapeutic effect of inhaled IFN-beta.