Light microscopic biopsy specimens from 48 patients were reviewed by two independent pathologists and classified as large cell carcinoma of the lung by 1981 World Health Organization (WHO) criteria. Sites of primary disease were hilar/mediastinal in 26 patients, large mid-lung field in 17, and peripheral lung in 5. All material was examined by electron microscopy (EM) for evidence of squamous ("squamous": 15 patients), glandular ("adenocarcinoma": 17 patients), or nonspecific ("large cell": 14 patients) ultrastructural differentiation. Two patients had mixed adenosquamous features. There were 6 patients with Stage I tumors; 5, Stage II; 24, Stage IIIM0; and 13, Stage IIIM1. Of the 14 patients with large cell by EM, 11 had unresectable Stage IIIM0 or metastatic disease. Only 3 of 27 patients not undergoing resection responded to combined modality therapy. There were two long-term survivors free of disease in the resected Stage IIIM0 patient category. Overall median survival by stage was analyzed, with no statistically significant difference between several of the stage groupings, suggesting a worse prognosis for the entire group overall compared to all patients with non-small cell lung cancer. The median survival by EM subgroup was also without significant difference, both overall and within various stage groupings, despite more patients in the large cell category with advanced disease. These data support the unique behavior of patients with large cell carcinoma on light microscopy, but fail to demonstrate that ultrastructural differentiation is of prognostic importance for response or survival.