In preparation for the use of bovine thymosin, a thymic hormone, as a specific T cell stimulator in immunodepressed patients, we studied its effect on E rosette formation of peripheral lymphocytes from patients with (1) advanced malignancies, (2) extensive burns, and (3) septicemia. E rosette formation in vitro with and without thymosin was evaluated in 52 patients with carcinoma of the breast (25) or lung (27) in relation to adjuvant therapy and/or surgery. The depression of E rosettes in cancer patients was most striking when adjuvant therapy, irradiation, and/or chemotherapy were used; in 20 patients this was elevated by incubation with thymosin. There was a delay in recovery of depressed E rosette levels after radical mastectomies in four patients, recovery being accelerated by thymosin. In ten burn patients (40 to 80 percent of body surface area, second and third degree burns), the depression in E rosette levels occurred in the first week and was most marked in 3 to 4 weeks. In eight patients this was elevated by thymosin in vitro. In four septic patients, all undergoing operation, serial studies suggested that recovery from sepsis was accompanied by spontaneous rise in E rosette levels. This process was accelerated by thymosin in vitro. This study as well as previous experiments with animals suggest that thymosin may influence depressed host resistance favorably by increasing T-cell-mediated immunity.