In this study, the susceptibility of porcine peripheral blood monocytes (BMo), peritoneal macrophages (PM phi) and alveolar macrophages (AM phi) to PRRSV was examined. To test the effect of differentiation and activation on their susceptibility, AM phi and BMo were aged, cultivated in either adhesion or suspension and treated with bacterial lipopolysaccharide (LPS) and phorbol myristate acetate (PMA). It was found that freshly isolated PM phi and BMo were non-permissive to PRRSV. PM phi remained refractory but a few BMo became susceptible after 1 day cultivation. AM phi were permissive with a significant increase of their susceptibility after one day cultivation. In a binding assay, it was demonstrated that the attachment of biotinylated PRRSV to AM phi is much more efficient than to PM phi and BMo. Two monoclonal antibodies (Mabs) 41D3 and 41D5 which block PRRSV infection of AM phi and are directed against a candidate receptor for PRRSV only reacted with the cell membrane of AM phi. PMA treatment of AM phi blocked PRRSV replication in the cells in a dose-dependent manner. The blocking effect of PMA decreased after 9 h continuous pre-treatment and diminished after 24 h continuous pre-treatment. PMA treatment did not affect the binding of PRRSV and MAb 41D3 and 41D5 to AM phi. Direct or indirect treatment of AM phi and BMo with LPS or cultivation in suspension did not significantly affect their susceptibility. These results provide clear evidence that PRRSV has a strongly restricted tropism for only some sub-populations of porcine monocytes/macrophages and that some specific states of differentiation and activation of monocytes/macrophages considerably affect their susceptibility.