Alveolar macrophages (AM) obtained both from specific viral antibody-positive (VA+) rats and from specific viral antibody-negative (VA-) rats were compared for their respective capacity to produce lipoxins (LX) in a given experimental condition. Both cell preparations were incubated with (15S), 15-hydroxy-5,8,11-cis-13-trans-eicosatetraenoic acid (15-HETE) in the presence of calcium ionophore A23187. The reaction mixtures were extracted and chromatographed on reverse-phase high performance liquid chromatography (RP-HPLC). Profiles of LX formation in each group were evaluated on the basis of chromatographic behavior, UV spectral characteristics (lambda max at 301 nm with shoulders at 289 nm and 317 nm), and co-elution with synthetic lipoxin A4 (LXA4) and lipoxin B4 (LXB4) standards as well as with authentic materials. The AM harvested from VA+ rats (AM-VA+) produced consistently detectable levels of LX (i.e., LXA4 and LXB4), whereas the AM from VA- rats (AM-VA-) produced no detectable LX under the same experimental condition. These results offer a possibility that elevated capacity of the AM-VA+ to produce LX may be associated with previous exposures to selected specific viral pathogens and/or with viral infections. Considering the distinct biologic properties of LX, the apparent production of the enhanced levels of LX as shown in this model system may play an important role in both pathophysiology and immunoregulatory network in virus-induced pulmonary disorder.