Post-weaning multisystemic wasting syndrome (PMWS), primarily caused by porcine circovirus type 2 -Us t\.I)(' 2 (PCV-2), is an economically important disease of pigs in many countries. A trial was designed to investigate the hypothesis that non-specific immuno-modulation can influence the clinical and pathological expression of PMWS in pigs naturally infected with PCV-2. Eighty-four pigs on a commercial pig farm were allocated to three groups of 28 pigs each, during an outbreak of PMWS. The pigs in the first group received an intramuscular injection of a vaccine against Mycoplasma hyopneumoniae (RespiSure(R), Pfizer, NY, USA) at each of 7 and 28 clays of age, followed by all intramuscular injection of normal saline at 12 days of age. The animals in the second group received, by intramuscular injection, normal saline at 7 days of age followed by a non-specific immuno-modulating drug (Baypamun(R), Bayer, Leverkusen, Germany) at each of 28 and 42 days of age. The pigs in the third control) group received an intramuscular injection of normal saline on each of 7, 28 and 42 days of age. The trial was concluded when the pigs had reached the age of 73 days. Clinical signs characteristic of PMWS developed in 42.9% of pigs inoculated with RespiSure(R) and in 50% of pigs treated with Baypamun(R); six pigs from each of these groups died. Moderate to severe gross and histopathological lesions of PMWS. associated with abundant PCV-2 antigen, were seen in a wide range of tissues of pigs from these groups at the end of the trial. In contrast, only 10.7% of pigs in the control group developed clinical signs and only one died. Mild to moderate lesions and scant PCV-2 antigen were occasionally observed in tissues of control pigs at the end of the trial. This is the first study to demonstrate that non-specific stimulation of the immune system by it vaccine or all immuno-modulatur drug can potentiate viral replication and increase the severity of clinical signs during an outbreak of PMWS. (C) 2002 Harcourt Publishers Ltd.