The relationships between the ''stress hormones'' corticotrophin (ACTH), vasopressin (AVP), corticotrophin releasing hormone (CRH) and cortisol, and the cytokines, interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor were studied during an acute infection. Ten patients (7 female, 3 male, age range 16-56 years) with acute pyelonephritis and normal renal function were studied during the first 72 hours following hospital admission. Peptide hormones were measured by radioimmunoassay, cortisol and cytokines by ELISA. Reference ranges for all hormones were from samples donated by 40 or more volunteers from the electoral roll. The reference data for IL-6 was obtained from 20 normal donor sera. The mean plasma IL-6, AVP and CRH concentrations on admission to hospital were significantly raised above the mean 08:00h values of the normal volunteers (p<0.001 for AVP and CRH, p<0.01 for IL-6), but mean plasma ACTH and cortisol were not. Mean plasma IL-6 and AVP were raised more than two standard deviations above the mean of the reference range for 72 hours, although IL-6 tended to fall after 24 hours. No change in plasma IL-1 and tumour necrosis factor was observed in three patients. The correlation between plasma IL-6 and cortisol concentrations at all sampling times and in all subjects was highly significant (p<0.001). Significant correlations between plasma IL-6 and AVP (p<0.005), and IL-6 and ACTH (p<0.05) were also observed. No correlation between IL-6 and CRH could be demonstrated. It was concluded that mean plasma levels of IL-6, AVP and CRH were significantly raised in patients with severe acute pyelonephritis on admission to hospital. Plasma concentrations of IL-6 correlated well with the ''stress hormones'' cortisol, ACTH and AVP, but not CRH. Although IL-6 may contribute to activation of the hypothalamic-pituitary-adrenal (HPA) axis during infection, this relationship requires further investigation.