Alveolar macrophage function is critical to the pulmonary immune response to infection. It is not known whether alveolar macrophages from HIV-infected individuals function normally in vivo. We have measured neopterin concentration, a marker of macrophage activation, in induced sputum, serum and saliva samples from control and HIV-infected subjects, with and without intercurrent lower respiratory tract infection (LRTI). Induced sputum (IS) neopterin concentration was increased in non-AIDS HIV positive (NAHIV) subjects (mean 3.5 nmol/l) compared to controls (mean 0.6 nmol/l) (P = 0.01) and it was further increased in patients with AIDS (mean = 27.7 nmol/l) (P = 0.002). When only those without LRTI were considered, the difference between the NAHIV and AIDS groups remained significant (P = 0.007). Those with LRTI had a significantly higher IS neopterin concentration (mean 53.2 nmol/l) than those without LRTI (mean 3.9 nmol/l) (P = 0.001). Contamination of the sample with saliva was not significant as there was no correlation between IS and saliva neopterin concentration (R = 0.1) and the concentration of neopterin was not related to the proportion of alveolar macrophages in IS samples (R = 0.2). Similarly there was no correlation between IS and serum neopterin concentration (R = 0.1). These results indicate that alveolar macrophages from NAHIV and AIDS subjects were in an activated state in vivo and that LRTI caused further stimulation (reflected in higher IS neopterin concentrations).