We determined the time-course of the production of transforming growth factor-beta (TGF-beta) after fluid-percussion injury using a bioassay. Biophasic production of TGF-beta composed mainly of TGF-beta 2 was detected in the ipsilateral cortex, with a first peak 30 min and a second peak 48 h after the lesion, flanking the transient production of tumor necrosis factor-alpha and interleukin-6 occurring between 5 and 18 h after trauma. This temporal pattern suggested that TGF-beta plays alternatively a pro- and anti-inflammatory role in the regulation of the brain cytokine network in response to injury, providing an endogenous mechanism for the control of the inflammatory reaction in traumatic brain injury.