One hundred-fourteen patients with inoperable adenocarcinoma of the lung (ACL) were evaluated by immunohistochemistry with monoclonal antibodies against Neuron Specific Enolase (NSE) and Chromogranin A (Chr A) in order to determine the frequency and prognostic impact of such antigen expression. All patients were previously untreated and received chemotherapy according to a prospective randomized trial. The tumors of 18 patients (16%) had more than 10% positive cells stained with anti-NSE, 59 (52%) had 1-10% positive cells and those of 37 patients (32%) contained no NSE-positive cells. The corresponding figures for Chr A were: 22 patients (19%), 51 patients (45%) and 41 patients (36%), respectively. Forty-four per cent of the patients with more than 10% positive NSE cells responded to chemotherapy (either complete or partial remissions) compared to 17% of the patients with fewer than 10% positive cells (p less than 0.025). The corresponding values for Chr A were 30% responders versus 19% responders (not statistically significant). The median survival for patients with more than 10%, 1-10% or no NSE-positive cells was 262 days, 231 days and 159 days, while, for Chr A it was 245 days, 200 days and 238 days, respectively. The survival curves for both NSE and Chr A according to the various levels of positivity were not significantly different. The presence of neuroendocrine marker in pulmonary adenocarcinoma seems to be associated with increased sensitivity to chemotherapy.