Although flow cytometry crossmatching is now performed by many kidney transplant centers, it yields a high false-positive rate, as evidenced in the present series by a 71% one-month success rate despite a positive crossmatch. In an attempt to reduce false-positive reactions while retaining the sensitivity of the flow cytometer, platelets were tested as targets. Whereas flow cytometry with T cells was not correlated with one-month failure rates, retrospective platelet crossmatching by flow cytometry showed that kidney failure within one month occurred in 53% of 19 patients with a positive platelet crossmatch compared with 15% of 48 patients with a negative platelet crossmatch. (P less than 0.002). Statistical significance in one-month outcome was also obtained when only first transplant patients were analyzed (P less than 0.04). The present results suggest that crossmatching with platelet targets may be a simpler way to avoid early primary nonfunction while minimizing false-positive reactions.