Stage III non-small cell lung cancer represents a broad spectrum of anatomical and histological subsets of patients with differing biological characteristics and prognostic expectations. Our experience with 161 consecutive patients undergoing complete resection for Stage III non-small cell lung cancer at the M. D. Anderson Hospital and Tumor Institute from 1965 through 1980 includes 69 patients with T3 N0 or N1 disease and 92 patients with an N2 classification. The cumulative 5-year survival overall was 30%: 35.6% for the T3 N0 or N1 group and 26% for the N2 patients. Seventy-three patients had squamous cell carcinoma and 76, adenocarcinoma. Small numbers of patients had other miscellaneous classifications (N = 12). In the T3 N0 or N1 subset, 43% of the patients with squamous cell carcinoma (N = 37) and 23% of those with adenocarcinoma (N = 25) survived 5 years. In the N2 subset, 39% of the patients with squamous cell carcinoma (N = 36) and 14% of the group with adenocarcinoma (N = 52) achieved long-term survival. Failure of treatment was clinically documented in 61 patients. The first observed recurrence or metastasis was at a distant site in the majority of these patients. Operative intervention for patients with Stage III M0 non-small cell lung cancer is effective and reflects the impact and limitations of resection on disease progression. Adjuvant irradiation was not shown to improve the outcome over the results of operation alone. Effective systemic therapy will be required to produce substantial changes in end results.