Antibody levels to pseudorabies virus (PRV) in cerebrospinal fluid (CSF) were compared to serum levels from immunized and infected pigs. Antibody was measured by single-dilution indirect solid-phase radioimmunoassay (IRIA). There was significantly higher CSF anti-PRV IgG relative to serum anti-PRV IgG (anti-PRV index, %) from infected pigs (1.390%, n = 14) than from vaccinated ones (0.141-0.149%, n = 5 and 7). The index from vaccinated and challenged pigs was intermediate (0.627%, n = 16), suggesting that vaccination cannot abrogate but can reduce the severity of encephalitis. Piglets with maternal antibody contained minimal CSF antibody similar to that of vaccinated animals. The CSF anti-PRV antibody was detected in piglets infected with as low as 10(2) TCID50 at 15 days postinfection. In infected pigs, the elevated CSF anti-PRV level was due to a leakage of serum antibody through a possible blood-brain barrier (BBB) impairment but not due to intrathecal antibody synthesis. Multiple regression analysis showed that the leakage was more time dependent than dose dependent. Leakage was detected until at least 4 weeks after disappearance of acute clinical symptoms. We have associated different levels of CSF anti-viral antibody with various infection or vaccination conditions.