Acute thermal burns result in impaired cellular immunity. This is reflected by an immediate lymphocytopenia, impaired delayed skin hypersensitivity, decreased allograft rejection potential, depletion of thymic dependent areas of lymphoid tissue, failure of peripheral blood lymphocytes (PBL) to respond to PHA, and a defect in both the response and stimulation capacity of PBL in mixed lymphocyte culture. The present study investigates the ultrastructure of the PBL of patients with acute thermal burns and correlates their morphology with the immunological defects previously shown to be present. Based upon their ultrastructural morphology, the PBL were divided into five cell types: small lymphocytes, large lymphocytes with dispersed ribosomes, large lymphocytes with aggregate ribosomes, large lymphocytes with varying amounts of rough endoplasmic reticulum, and plasma cells. The serial studies performed in 14 adult burn patients were compared with similar studies performed in a group of 15 normal controls. On the first day post-burn, the PBL profile did not differ significantly from that of a normal group of adults although the lymphocyte count in peripheral blood was already decreased. By the second day a significant shift in the morphology of the PBL towards cells having larger quantities of rough endoplasmic reticulum had occurred coincident with a marked fall in the percentage of small lymphocytes present. With the passage of time this change became more pronounced. By 6–10 days post-burn, a mean of more than 30% of the PBL could be identified as either immature or mature plasma cells. Following this time of maximal change a return toward normal was seen, so that by Day 21–23 post-burn, the PBL profile had returned to essentially normal values. A comparison of these studies with other studies performed on patients with acute thermal burns makes it apparent that in the immediate post-burn period a marked defect in cellular immunity or T-cell function occurs simultaneously with a marked stimulation in humoral immunity or B-cell function. The latter abnormality is reflected by the development of a polyclonal gammopathy and the development first of a marked B-lymphocytosis followed by a marked plasmacytosis coincident with the return of PBL counts to normal. The mechanisms causing these changes in the burn patient are not known.