This long-term study includes up to 13 years of follow-up on 56 patients who underwent surgical resection of nonsmall cell lung cancers (NSCLC) at the University of Texas Medical Branch. The purpose of this study was to investigate whether p53 and P-glycoprotein expression in the tumor correlates with survival. The study included 35 men and 21 women with mean age at diagnosis of 63.6 years and 58.0 years, respectively. Follow-up ranged from four to 156 months (mean, 52 mo). Actual five-year survival was 50% and 10-year survival was 22%, There were 25 patients who survived more than 60 months. Commercially available antibodies, DO-7 monoclonal antibody to p53 protein, and NCL-PGLyp polyclonal antibody to P-glycoprotein were used. p53 expression was seen in 45%, and P-glycoprotein expression was seen in 61% of the tumors, using standard immunohistochemical techniques. Expression of p53 showed correlation with Caucasian race and a better, although nonsignificant, five-year survival. P-glycoprotein expression showed a highly significant association with squamous cell carcinoma. No association was found between P-glycoprotein expression and survival. A negative association was seen between p53 and P-glycoprotein expression. Using nonparametric analysis, significant correlations were found between female sex and younger age at diagnosis of lung cancer compared with males, adenocarcinoma, and Caucasian race. Using Kaplan-Meier survival tables, significantly better five-year survival was seen with stage I tumors, negative lymph nodes at surgery, Caucasian race, and well-differentiated tumors. Stage I and negative lymph nodes at surgery showed an independent significant association with long-term (>5-yr) survival. This study indicates that p53 and P-glycoprotein may not be useful as immunohistochemical markers for guiding therapy and predicting survival in NSCLC.