We have previously described alterations in pulmonary alveolar macrophage (PAM) function in patients with lung cancer when compared with control subjects. This study examined PAM from five patients with lung cancer, seven normal volunteers and nine control patients, to assess whether any differences in surface phenotypic markers were present in lung cancer versus non-cancer subjects, and what changes might be induced with interferon-gamma (IFN-gamma) stimulation. After 3 days' culture with or without IFN-gamma no differences were seen in the percentages of cells staining positively in each group for HLA class I, class II and ICAM-1 (CD54) antigens. However, in 13 out of 14 control subjects, and only one out of the five cancer subjects, dual PAM populations were identified. The second PAM population (PAM-2) was larger and demonstrated a higher expression of class I and ICAM-1 antigens. Unlike the unfractionated PAM population, PAM-2 consistently responded to IFN-gamma stimulation with an increase in both class I (90 +/- 25%) and ICAM-1 (45 +/- 10%) antigens, while there was no change in class II antigen expression. In three subjects PAM-2 was found to induce a significantly greater mitogen response than the rest of the PAM population. If confirmed in a larger group of patients, the absence of PAM-2 in the majority of patients with lung cancer may underlie the functional PAM defects observed in these patients.