Objective. To study cortisol, adrenocorticotropic hormone and C-reactive protein responses to specific stimuli in familial Mediterranean fever (FMF). Methods. For the purpose of measuring cortisol, ACTH, and CRP responses to insulin induced hypoglycaemia during attack-free periods, 14 FMF patients, 11 patients with ankylosing spondylitis or Behçet's disease as disease controls (DC), and a further 10 healthy control subjects (HC) were involved in this study. None of the subjects had ever received corticosteroids before this study. Cortisol and ACTH levels were measured by chemiluminescence enzyme immunoassay. Results. No attack was observed among FMF patients during the test. No significant difference in the mean cortisol values after insulin induced hypoglycaemia was observed between the groups involved at any stage of the test. The integral cortisol response to hypoglycaemia expressed as the AUC (0-90 min) was found not to differ among the study groups (1827 ± 115.6 in FMF; 2196 ± 205.4 in DC, p = 0.12; 1771 ± 98.4 in HC, p = 0.9). The delta response of cortisol to insulin induced hypoglycaemia was found to be statistically lower (-4 ± 0.8 mg/dl vs. -1.9 ± 0.7 μg/dl; p < 0.03) only for the 0 to 30 min interval in patients with FMF compared to HC respectively. Similar results, though of no statistical significance, were also found for the 0 to 45 min interval (1.17 ± 2.2 μg/dl in FMF patients vs. 3.3 ± 2 μg/dl in HC; p = 0.6). The mean basal CRP level of patients with FMF was remarkably higher than that in HC. Although the mean CRP level at 90 min for FMF cases with cortisol levels under 12 μg/dl at 30 min was found to be higher than those with cortisol levels over 12 μg/dl at 30 min, no significant difference was observed. Conclusion. An early blunted cortisol response observed in a stressful situation in FMF patients may well account for the curious relationship between stress and an inflammatory reaction and/or attack. Furthermore, the fact that the CRP level was relatively higher in FMF patients with lower cortisol levels might also highlight the importance of endogen cortisol in the inflammatory feature of this disease.