Background: Both cortisol and thyroid hormones were sought to be stress hormones in critical illnesses which are readily measurable in a clinical setting. The investigation was to sequentially observe the changes in these hormone levels in pigs after acute radiation exposure. Methods: Six 27-week-old SPF miniature pigs were divided into 2 groups. The irradiated (non- survival) group (n =4) received 12 Gy of 60Co whole body γ-irradiation only and all died within 3 weeks after irradiation. The non-irradiated group C (n=2) served as control. Serial blood samples were drawn at the same time the day before and weekly after irradiation for 7 weeks. Results: A trend of progressive decline of both serum T3 and T4 values after irradiation was found. A rapid drop of serum tri-iodothyronine (T3) values was found in the irradiated groups, which is reaching the nadir within 10 days post-irradiation. There was a profound decrease of T4 values in the irradiated group days before death (all ＜23 nmol/L, 49% mean decrease before death, control, 31-44 nmol/L). Changes of serum cortisol values were rather inconsistent in irradiated groups. There was a surge of serum cortisol value in the irradiated group within 2 days before death (167 ± 122 vs. 453 ± 177 nmol/L; P＜0.01) that was not found in the control group (195±34 nmol/L). Conclusion: Serial monitoring serum T3, T4 and cortisol values may be a feasible indicator of the severity of acute radiation events. Dropped T3 levels appeared to be a sensitive marker to reflect the presence of sickness while the degree of decrease of serum T4 levels may represent the severity of sickness. A surge of serum cortisol value may indicate a fatal outcome.