Summary: Large skin grafts were exchanged orthotopically between 29 pairs of unrelated female albino rats. The sera of these animals were tested for a skin reaction producing factor (SRPF) similar to that described in a previous paper on rat parabiosis. The sera of 17 rats out of 58 tested produced skin reactions when injected intradermally into the respective graft donor but always failed to produce a skin reaction in the animal itself. The sera which elicited a positive skin reaction in the graft donor also frequently produced positive results in other unrelated rats. In contrast, those sera which failed to elicit a skin reaction in the graft donor gave consistently negative results in other animals. The skin reactions described in this paper were considered to be due to isoantibodies directed against the tissue constituents present in the skin of the graft donor but absent from the recipient of the graft.