Objective: To investigate the Growth Hormone (GH)/Insulin-like Growth Factor-I (IGF-I)axis and identify the factors that determine IGF-I levels in adult septic patients of variable severity,i.e., with sepsis, severe sepsis or septic shock, in the acute phase of disease.Design: Prospective study comparing septic patients treated in a general intensive care unitand healthy volunteers.Methods: In 107 consecutive septic patients (44 with sepsis, 13 with severe sepsis, and 50with septic shock), GH, IGF-I, Insulin-like Growth Factor Binding Protein-3 (IGFBP-3), insulin,cortisol, albumin, thyroid hormones, C-reactive protein and interleukin-6 serum levels weremeasured once within 48 hrs after onset of a septic episode. Twenty-nine healthy volunteers servedas controls.Results: IGF-I and IGFBP-3 levels were decreased in patients with sepsis and severe sepsis(versus controls), decreasing further in patients with septic shock (versus sepsis). IGF-I levels were positively related to IGFBP-3, albumin, triiodothyronine and thyroxine, and inversely related to cortisol, sepsis severity, C-reactive protein, interleukin-6 and age. In multiple regression analysis, IGF-I levels were independently related to IGFBP-3 and albumin (lower in patients with decreasedIGFBP-3 and albumin levels) (p<0.001 and p=0.01, respectively), and cortisol (lower in patientswith increased cortisol levels) (p=0.04). IGFBP-3 accounted for most of the variance explained bythe model (R2=0.519). GH levels were not related to IGF-I levels or mortality. IGF-I and IGFBP-3levels were associated with mortality.Conclusions: The GH/IGF-I axis is severely disrupted in septic patients. IGFBP-3 is themajor determinant of IGF-I levels, whereas albumin and cortisol are secondary determinants.