Virulent classical swine fever (CSF) represents an immunomodulatory viral infection that perturbs immune functions. Circulatory and immunopathological disorders include leukopenia, immunosuppression and haemorrhage. Monocytic cells - targets for CSF virus (CSFV) infection - could play critical roles in the immunopathology, owing to their production of immunomodulatory and vasoactive factors. Monocytes and macrophages (Mphi) are susceptible to virus infection, as a consequence of which prostaglandin E2 (PGE2) production is enhanced. The presence of PGE2 in serum from CSFV-infected pigs correlated with elevated PGE2 productivity by the peripheral blood mononuclear cells from these same animals. It was noted that these PGE2-containing preparations did not inhibit, but actually enhanced, lymphocyte proliferation. The proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 were not involved, although elevated IL-1 production could relate to lymphocyte activation. Nevertheless, IL-1 was not the sole element: infected Mphi produced lympho-stimulatory activity but little IL-1. This release of immunomodulatory factors, following CSFV infection of monocytic cells, was compared with other characteristics of the disease. Therein, PGE2 and IL-1 production was noted to coincide with the onset of fever and the coagulation disorders typical of CSF. Consequently, these factors are of greater relevance to the haemorrhagic disturbances, such as petechia and infarction, rather than the leukopenia found in CSF.