A total of 71 patients with extensive small cell lung cancer were enrolled in CALGB study 8733. Chemotherapy was administered with cisplatin 33 mg/m2, i.v. infusion days 1-3, doxorubicin 45 mg/m2 i.v. day 1, cyclophosphamide 800 mg/m2 i.v. day 1, and etoposide 80 mg/m2 i.v. infusion days 1-3 (PACE). Following four courses of PACE, patients achieving a CR or PR were started on recombinant interferon-gamma (rINF-gamma) 0.2 mg s.c. daily until grade IV toxicities or progression occurred. Of the 71 patients enrolled, 67 are evaluated (47 males and 20 females), median age 59 years, and median PS1. The response rate to PACE was 48/67, 72%. Grade 3-4 toxicities included granulocytopenia, thrombocytopenia, and five treatment-related deaths (7%). Forty-one patients were started on rINF-gamma. Of these 41 patients, 11 were in CR, 30 in PR. The objective response rate to rINF-gamma was 2/30 or 6.7%. Recombinant rINF-gamma is inactive in small cell lung cancer, even when the tumor burden has been substantially reduced by prior chemotherapy.