The biological half-life of exogenous [4-14C] cortisol in guinea pigs is approximately 105 min. After ovariectomy there is a tendency to a prolonged half-life (delayed metabolism) of cortisol. The plasma cortisol in guinea pigs is 314 ± 79 ng/ml with an ultrafiltrable fraction of 38 ± 15 ng/ml. Skin cortisol is 44 ± 12 ng/g tissue. After ovariectomy the plasma cortisol is decreased (195 ± 36 ng/ml) and there is a higher relative diffusible fraction, while the skin cortisol is decreased (23 ± 4 ng/g). During stress release there may be a parallel release of a cortisolbinding non-ultrafiltrable component or an elimination of a protein bound not fluorescent or separated steroid. The tissue cortisol is higher than would be expected from the values of diffusible cortisol in plasma. The low concentration of ultrafiltrable cortisol may explain the reduced rate of cortisol metabolism.