Background: TGF-beta and IGF-I are particularly important to collagen synthesis and angiogenesis in wounds. Little is known of their expression in human wounds. Methods: This clinical study investigates TGF-beta and IGF-I expression in wound fluid and wound tissue samples of two groups of healing wounds, both treated with vacuum sealing technique (Vacuseal(R)). Group 1 wounds were acute and non infected (fasciotomy, n = 6) and group 2 were older/chronic (over 4 weeks) and have been infected (n = 10). Fluid samples were taken on days 1,4, 7 and 14. Tissue samples were taken on days 1, 7 and 14. TGF-beta 1, TGF-beta 3 TGF beta RII, IGF-I and IGF-IR mRNA expression of wound tissue were examined with RT-PCR. IGF-I and ICE-binding proteins (IGFBP) in the wound fluid were measured by a standard radioimmunoassay (RIA). The proteolytic degradation of wound fluid was determined by protease assay using radiolabeled IGFBP2 or IGF-I. Total protein was analysed by Biuret method. Results: Wound fluids in both groups contained similar amounts of ICE-I, IGF-binding protein 2 (IGFBP2) and IGFBP3. However, proteolysis of ICE-I and IGFBP2 was not detected in group 1 wounds, but was elevated in group 2. TGF-beta 1, TGF-beta RII, IGF-I and IGF-IR mRNA expression were also elevated in group 2. TGF-beta 3 expression was similar in both groups. Conclusions: Clinical therapies which extract fluid from wounds allow an unprecedented opportunity to study wound healing. There are significant differences in TGF-beta 1, TGF-beta RII, IGF-I and IGF-IR expression between older/infected and new/noninfected wounds. Contrary to expectations non infected wounds showed no expression for IGF-I and IGF-IR. The only significant source of ICE-I early in the healing course of non infected wounds appears to be blood.