Introduction: The occurrence of severe sepsis may be associated with deficient pro-inflammatory cytokine production. Transforming growth factor b-1 (TGFb-1) predominantly inhibits inflammation and may simultaneously promote IL-17 production. Interleukin-17 (IL-17) is a recently described pro-inflammatory cytokine, which may be important in auto-immunity and infection. We investigated the hypothesis that the onset of sepsis is related to differential TGFb-1 and IL-17 gene expression. Methods: A prospective observational study in a mixed intensive care unit (ICU) and hospital wards in a university hospital. Patients (59) with severe sepsis; 15 patients with gram-negative bacteraemia but without critical illness and 10 healthy controls were assayed for TGFb-1, IL-17a, IL-17f, IL-6 and IL-1b mRNA in peripheral blood mononuclear cells (PBMC) by quantitative real-time PCR and serum protein levels by ELISA. Results: TGFb-1 mRNA levels are reduced in patients with bacteraemia and sepsis compared with controls (p = 0.02). IL-6 mRNA levels were reduced in bacteraemic patients compared with septic patients and controls (p = 0.008). IL-1b mRNA levels were similar in all groups, IL-17a and IL-17f mRNA levels are not detectable in peripheral blood mononuclear cells. IL-6 protein levels were greater in patients with sepsis than bacteraemic and control patients (p < 0.0001). Activated TGFb-1 and IL-17 protein levels were similar in all groups. IL-1b protein was not detectable in the majority of patients. Conclusions: Down regulation of TGFb-1 gene transcription was related to the occurrence of infection but not the onset of sepsis. Interleukin-17 production in PBMC may not be significant in the human host response to infection.