Serum sickness in man may occur after treatment with foreign proteins such as tetanus or diphtheria antisera, and in some patients leads to neurological complications such as neuropathy or encephalomyelitis. Many of the effects of serum sickness are associated with the deposition of antigen-antibody complexes in the tissues. Chronic serum sickness in the rabbit has previously been shown to cause perivascular inflammation and demyelination in the nervous system. We induced chronic serum sickness in the Lewis rat by daily intraperitoneal injections of bovine serum albumin (BSA) in male rats that had previously received footpad inoculations of BSA. Two animals died of anaphylaxis and 15 were observed for periods of 39 to 142 days. Three animals injected with 3 mg or 4 mg/day of BSA, and 6 animals injected with up to 16 mg/day of BSA had no clinical abnormalities when sacrificed. Six animals were injected with 36 to 40 mg BSA/day and, at the time of sacrifice, were lethargic and had ruffled fur, but no neurological signs. In these animals, the production of chronic serum sickness was confirmed by the presence of immune complex deposits in the kidneys. In the nervous system, there was no evidence of inflammatory cell infiltration either in the parenchyma or the vessel walls. Immunofluorescence studies identified deposits of immunoglobulin in the choroid plexus of chronic serum sickness rats but not in controls. Staining with antibodies to immunoglobulin, complement and BSA showed marked staining of blood vessels of the nerve roots of the animals with chronic serum sickness.(ABSTRACT TRUNCATED AT 250 WORDS)