A commercial swineherd in Indiana experienced high death loss of nursery pigs with neurologic disorders for a prolonged period. Polioencephalomyelitis was the consistent histopathological lesion in affected animals. A porcine enterovirus (PEV) classified to group I was isolated from spinal cords and brains collected from the affected animals. The isolate (ISUVDL 200103183) was determined to belong to either serogroup 5 or 6 at the National Veterinary Services Laboratories, Ames, IA. No other significant viral or bacterial agents were isolated from or detected in the animals. A prospective longitudinal serological monitoring of pigs in the index herd for the PEV isolate revealed that colostrum-derived neutralizing antibodies to the virus rapidly declined, and by the age of 21 days the majority of piglets had no or minimal neutralizing antibody against the virus. Seroconversion to the virus then coincided with increased mortality in the herd. Results of diagnostic and cohort observations supported a diagnosis of PEV infection as the cause of the prolonged outbreak of "polio." Investigation into factors that may be contributing to the prolonged problem is currently in progress.