The cause and timing of first liver allograft failure was evaluated in 177 patients who underwent a second liver transplant between January 1984 and December 1988. The population studied consisted of 94 men and 83 women with a mean age 41.3 +/- 1.0 yr (mean +/- S.E.M.). Mean first-graft survival was 130.6 +/- 22.9 days (range = 0 to 2,073 days). Sixty-eight percent of the grafts failed in the first postoperative month, 26% failed between the second and twelfth month and only 6% failed beyond the twelfth month from the date of the initial transplant. Six principal causes of graft failure were identified. Early allograft losses occurred as a result of four major problems: primary graft nonfunction (30.0% of all grafts; mean graft survival = 3.4 +/- 0.3 days); ischemic injury of the graft without overt vascular injury (9.6%; mean graft survival = 17.5 +/- 1.9 days); acute rejection (10.7%; mean graft survival = 30.4 +/- 6.4 days); and overt vascular complications (26.6%; mean graft survival = 59.6 +/- 24.1 days). Late graft failures were the result of either chronic rejection (11.3%; mean graft survival = 496.3 +/- 136.0 days) or recurrence of the primary liver disease (6.8%; mean graft survival = 550.5 +/- 172.1 days). Graft failure occurred as a result of a variety of miscellaneous causes in 5% of the cases (mean graft survival in this group = 300.0 +/- 110.6 days). Overall 6-mo patient survival after a second liver transplant was 46.3%.(ABSTRACT TRUNCATED AT 250 WORDS)