Modulation of intercellular adhesion molecule 1 (ICAM-1) expression on alveolar macrophages (AM) may be one of the the basic mechanisms by which AM regulate the course of inflammatory response during pulmonary allograft rejection and infectious processes by mediating macrophage-lymphocyte interactions. As a model for studying anti-inflammatory activity of drugs on AM, we have investigated the effect of fusafungine, a local antibiotic which displays also anti-inflammatory properties, on the regulation of ICAM-1 membrane expression induced in vitro by stimulating AM from lung-transplant recipients. We have studied ICAM-1 membrane expression by immunocytofluorometric analysis using the anti-CD54 monoclonal antibody. The ICAM-1 molecule was expressed on 10 to 47% of freshly isolated AM, depending on the clinical status of the patients. After 24 hr cultivation with 250 U/ml gamma-IFN, the percentage of ICAM-1+ AM s increased to more than 90%. When added with the stimulating agent, fusafungine could inhibit the induction of ICAM-1 membrane expression, up to 90% of inhibition at 8 microgram/ml. However, once ICAM-1 was induced after 24 hr cultivation upon stimulation, fusafungine could not afford any reversion. On going investigations on mRNA for ICAM-1 should indicate whether fusafungine acts at the transcriptional level. These results clearly demonstrate the capacity of fusafungine to down-regulate ICAM-1 expression on AM upon activation. This approach could represent a useful tool for in vitro study of drug efficacy upon inflammatory processes of the respiratory mucasa.