The effects of mild inflammation induced by topical chloroform treatment on plasma extravasation and mast cell response were studied in normal innervated and denervated rat skin. In the absence of inflammation, the reduction in plasma protein extravasation in response to noxious heat was 31.2% in denervated skin compared to the innervated skin. In the presence of inflammation, the reduction in this response was 52.5% in denervated skin compared to the innervated skin. During inflammation, mast cells became abundant, highly degranulated and migrated to the lower dermal tissue forming large aggregations. The ultrastructural observations showed a close anatomical relationship between mast cells and vesicle-containing nerve profiles. These results indicate that repeated topical chloroform treatment of the rat skin induces neurogenic vascular inflammation accompanied by an increase in mast cell response.