The purpose of the study reported here was to determine the prevalence of porcine reproductive and respiratory syndrome virus (PRRSV) in pigs affected with post-weaning multisystemic wasting syndrome (PMWS), a disease believed to be caused by porcine circovirus type 2 (PCV2). From May 1997 to February 2000, PMWS was diagnosed in 277 pigs (from 120 farms) submitted to the Veterinary Pathology Diagnostic Service, Veterinary School of Barcelona, Spain. In each case, the PMWS diagnosis was based on clinical history and the detection, by in situ hybridization, of nucleic acid of PCV2 in characteristic histologic lesions. Antigens for PRRSV were detected by immunohistochemistry in tissues of 66 (23.8%) of the same 277 pigs. Sera, which were available for 93 of the 277 pigs, were tested for PRRSV by a multiplex reverse transcription-polymerase chain reaction (RT-PCR). A total of 33 of these sera were RT-PCR positive, three for a North American strain(s) of PRRSV. In addition, 76 of the 93 sera were tested for antibodies to PCV2 (indirect immunoperoxidase) and PRRSV (enzyme-linked immunoassay). Antibodies for PCV2 and PRRSV were detected, respectively, in 56 (73.9%) and 43 (56.6%) of the 76 sera. Collectively, these results suggest that while infection with PRRSV may be common, it is not an essential component of PMWS.