Immunofluorescence staining of donor skin with recipient serum was performed in 25 patients undergoing kidney transplantation. Transplants were performed when cytotoxicity T cell crossmatches with long incubation and with antiglobulin enhancement were negative. In 20 patients the skin crossmatch was negative and all had an uneventful course. In 5 other recipients, the crossmatch with skin was positive and all developed severe rejection 1–8 days after transplantation. The correlation between skin crossmatch and early rejection was statistically highly significant (P< 0.00001). Rejection in the skin-crossmatch—positive group led to graft loss in 3, and chronic rejection with poor residual function in the other 2 patients. Serum creatinine at one month was in the 2.6–5.0 mg/dl range in these two patients, while in the group with negative skin cross-matches 15 had serum creatinine levels of less than 1.6, and 5 were in the 1.6–2.5 mg/dl range. Although the nature of the skin antigen is unknown, it appears that this crossmatch procedure was highly accurate in predicting early kidney transplant rejection.