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Cortisol metabolism was studied in conscious adult male guinea-pigs subjected to a neurotrophic stress (immobilization and stimulation by light for 3 h).

The disappearance curves of tracer quantities of [³H]cortisol were represented by a two-pool model. In stressed animals, there was a marked increase in the mean plasma level of cortisol (184% of control value; P <0·001) and in the metabolic clearance rate (MCR; 17% of control value; 0·001 <P <0·01). This rise in the MCR of plasma cortisol resulted from an increase in the mean total apparent volume of distribution (49%, P < 0·001). The lack of significant differences in the slopes of the second exponential phase of the disappearance curves indicated that the stress did not significantly increase the half-life of cortisol. The mean binding capacity of transcortin for cortisol (S_T) was significantly higher in the animals which had been subjected to the neurotrophic stress than in the control guinea-pigs (0·02 < P <0·05). However, S_T values remained very low and accounted for the very high levels of free cortisol found after the stress. The results suggest that the raised concentrations of unbound cortisol found in the plasma of conscious adult male guinea-pigs in response to neurotrophic stress reflect a hypersecretion of corticosteroid.