Fifteen patients with previously untreated, inoperable non-small cell lung cancer were treated with r-IFN-gamma 2 mg/m2, on alternate days three times a week for a maximum of 12 weeks. After IFN treatment patients with stage III a + b disease received radiotherapy (55 Gy/44 F/32 d b.i.d.), and 4/5 patients with stage IV disease received chemotherapy (cisplatin-vindesine). Ten patients were evaluable for response at 4 weeks; 9 had stable disease and one had progressive disease. At 12 weeks 7 patients were evaluable; one had a partial response, and 6 had stable disease. Of 10 patients subsequently given radiotherapy 2 achieved CR, 5 PR, and 3 SD. Of the 3 evaluable patients receiving chemotherapy 1 PR, 1 SD and 1 PD were observed. IFN-gamma treatment was discontinued due to toxicity in 7/15 of patients. Main toxicities were the 'flu'-like syndrome (in 15 patients) and cardiovascular events (in 13 patients). Three patients were withdrawn because of cardiotoxicity. Our results suggest that high dose r-IFN-gamma might have some biological activity in NSCLC and does not interfere with subsequent conventional therapies given with a curative intent.