Experimental autoimmune neuritis (EAN) is a CD4(+)T cell-mediated demyelinating disease of the peripheral nervous system (PNS) and serves as an experimental model for human immune-demyelinating neuropathies. In this study, we examined the effect of recombinant rat interleukin-4 (rrIL-4) on chronic EAN in Lewis rats induced by immunization with P0 peptide 180-199 and complete Freund's adjuvant (CFA). We estimated that nasal administration of rrIL-4, in dose ranges of 0.1-1 microg/rat/day in the initial phase of EAN, decreased the severity and the duration of clinical EAN. Hyporesponsiveness of T cells, downregulation of Th1 cell responses (INF-gamma), but increased levels of specific IgG1 isotypes document that nasal administration of rrIL-4 was systemically immune effective. Low grade inflammation and complete lack of regional demyelination within the sciatic nerves were seen in rrIL-4 treated rats. Based on these observations we suggest that nasal administration of IL-4 could be further evaluated, considering its possible use in human immune-demyelinating neuropathies.