FK 506 was tested in unrelated baboons submitted to renal transplantation and bilateral native nephrectomy. Untreated baboons died after 9.2 +/- 4.0 SD days. When FK 506 was given orally for 90 days, survival with the optimum dose was 74.6 +/- 28.9 days; this allowed maximum credit for each individual animal of 90 days. A 3-day course of intramuscular FK 506 started on postoperative day 4 allowed 1- to 2-month survival. Delayed rejection in these baboons as well as in those treated daily for 90 days with FK could sometimes be reversed temporarily with a second 3-day course. The doses required for a good therapeutic effect were 10 times greater in baboons than in dogs, a finding that may reflect a species difference of lymphocyte sensitivity to this drug. FK appeared to be relatively nontoxic in subhuman primates, and it remains a promising drug for clinical trial.