Depletion of T cell subsets with monoclonal antibody (mAb) permits analysis of cellular events mediating allograft destruction. Mab OX-19 and mAb OX-8 were used singly and in combination together with a short pretransplant course of cyclosporine A (CsA) to deplete OX-19+ cells (all T cells) and OX-8+ cells (cytotoxic/suppressor and NK cells), respectively, in diabetic Lewis (Lew) recipients of a Wistar Furth (WF) pancreatic allograft. Depletion of lymph node T cell subsets was assessed at rejection (blood sugar greater than 250 mg/dl) by flow cytometry. Untreated Lew recipients (Group 1) rapidly rejected their allograft (11.5 +/- 2.5 days). MAb OX-19 administration on the day prior to surgery (Day -1), on the day of surgery (Day 0), and alternate days thereafter until rejection (Group 2) prolonged graft survival (15.0 +/- 1.6 days, P less than 0.05). MAb OX-19 administration on alternate days beginning 14 days prior to transplantation (Day -14) until rejection (Group 3) further prolonged graft survival (22.6 +/- 3.4 days, P less than 0.01). At rejection large numbers of OX-19+ cells were present in both groups. Administration of mAb OX-8 alone (Group 4) failed to prolong graft survival despite marked depletion of OX-8+ cells at rejection. Administration of mAb OX-19 from Day -14 together with CsA (15 mg/kg) from Days -14 to -8 inclusive (Group 5) resulted in a marked and sustained depletion of OX-19+ cells at rejection but only a modest prolongation of graft survival (27.6 +/- 6.0 days, P = 0.11). CsA alone from Days -14 to -8 failed to prolong graft survival.(ABSTRACT TRUNCATED AT 250 WORDS)