Immunologic factors that predict survival in patients with lung cancer have not been established. We examined the relationship between the percentage of HLA-DR-positive peripheral leukocytes [HLA-DR+ (%)] and survival of patients with squamous cell carcinoma of the lung. Before initiating therapy, peripheral blood was taken from 105 patients with squamous cell carcinoma of the lung. HLA-DR positivity was determined by flow cytometry. Patients were divided into 2 groups; a high and a low percentage group. The significance of the intergroup difference in the Kaplan-Meier survival curves was determined by the log rank test. Multivariate analysis was performed using the Cox proportional hazards model. The average HLA-DR+ (%) was 25.9 +/- 10.6% (mean +/- SD). Survival in the high percentage group (HLA-DR+ (%) > or =25.9%, n=44) was much worse than that in the low percentage group (HLA-DR+ (%) <25.9%, n=61; p=0.0002). The 5-year survival rate in the high percentage group was only 7.4%, while that in the low group was 54.3%. Multivariate analysis identified a significant association between survival and lymph node metastasis (p=0.0028) and HLA-DR+ (%) (p=0.0004). Survival of patients with stages I, II, and IIIA was worse in the high percentage group (n=32) than that in the low percentage group (n=43; p<0.0001). However, survival of patients with more advanced disease, stages IIIB and IV, was similar in the high percentage (n=12) and low percentage groups (n=18; p=0.7610). The peripheral HLA-DR+ (%) predicts survival of patients with resectable squamous cell carcinoma of the lung.