mdash;: A severe thermal injury is commonly associated with immune suppression and increased susceptibility to sepsis, frequently leading to multiple organ failure. Transforming growth factor-beta (TGF-[beta]) is a potent immunosuppressive cytokine involved in complications associated with major trauma. Interleukin-4 (IL-4) is thought to synergize the immunosuppressive activity of TGF-[beta] by promoting naive lymphocytes to differentiate and generate TGF-[beta] secreting cells. This study examines the alterations in serum levels of TGF-[beta] and IL-4 after a thermal injury. Male Sprague-Dawley rats (300-400 g) were anesthetized and received a 50% total body surface area full-thickness scald burn followed by fluid resuscitation and analgesia. Control rats were given the same treatment, but were immersed in water at room temperature. Rats were sacrificed from 1 h to 8 days after injury. Blood samples were collected aseptically from the inferior caval vein. Serum levels of TGF-[beta] and IL-4 were measured by enzyme linked immunosorbent assay. Rats in the control and thermal injury groups showed similar increases in serum TGF-[beta] 1 h after injury. A progressive increase in serum TGF-[beta] was observed in burned animals compared to control animals starting on day 3 and continued through day 8 (P< 0.01). Serum IL-4 levels in control and thermally injured animals remained undetectable (< 15.6 pg/mL) throughout the experiment. Thermal injury induces a significant increase in serum TGF-[beta], which may contribute to post-burn immunosuppression with an increased susceptibility to sepsis.