An acute renal transplant rejection episode has been shown to be associated with decreased 1-year graft survival. The impact on long-term outcome is undefined. We studied the impact of an acute rejection episode on t1/2, the time it takes for 1/2 of the grafts functioning at 1 year to fail. Use of t1/2 avoids inclusion of early graft loss to acute rejection or complications of treatment. Since 1/1/86, a total of 653 patients have received a primary kidney transplant and had at least 1 year of function. Recipients were divided by the incidence and timing of rejection: no rejection; 1 rejection within the first year; > 1 rejection, the first episode in the first year; and > or = 1 rejection, the first episode after the first year. A single rejection episode in the first year reduced t1/2 (45 +/- 11 years in those with no rejection vs. 25 +/- 8 years in those with 1 in the first year). Multiple rejections (t1/2 = 5 +/- 11 years) and a first rejection after the first year (t1/2 = 3 +/- 1 years) have a significant effect (P < .05). Both living and cadaver donor recipients with rejection had shortened t1/2. For those with > 1 rejection, the first episode in the first year, and those with > or = 1 rejection, the first episode after the first year, chronic rejection was the predominant cause of graft loss; noncompliance also played a role. We conclude that a single rejection episode shortens t1/2. Those with > 1 rejection, the first episode within the first year, and those with > or = 1 rejection, the first episode after the first year, are at high risk for late graft loss.