To clarify the significance of the role of the immune system in the formation of proliferative burn scars, this study attempted to identify differential production of cytokines between patients with burn injuries with and without hypertrophic scars. Mononuclear cell fractions were isolated from the peripheral blood (PBMC) of each patient and incubated with and without antigenic or mitogenic stimulation. The resultant supernatants were then assayed by ELISA techniques for production of various cytokines. The production of IL-1, IL-6, TNF-alpha, and TGF-beta2 by unstimulated PBMC was elevated significantly in patients with proliferative scar compared to control patients. Production of TGF-beta2 by stimulated PBMC also was elevated significantly in patients with proliferative scar. This study suggests that an increase in the production of TGF-beta and of proinflammatory cytokines by mononuclear cells may play a significant role in the processes that lead to excessive scar formation after burn injury.