The kinetics of prednisolone after intravenous prednisolone and oral prednisone were investigated in 19 young (23 to 34 years) and 12 elderly (65 to 89 years) subjects. The systemic availability of unbound prednisolone after oral prednisone and the apparent interconversion of prednisolone into prednisone and vice versa (reflecting the activity of the 11 beta-hydroxydehydrogenase) were independent of age. The total exposure of the elderly subjects to prednisolone was increased because the nonrenal (5.7 +/- 1.0 vs. 7.7 +/- 1.6 ml/min/kg, mean +/- SD; P less than 0.001) and renal (0.9 +/- 0.3 vs. 2.9 +/- 0.7 ml/min/kg; P less than 0.001) clearances of unbound prednisolone were lower in the elderly. The fractional clearance of 6 beta-hydroxyprednisolone (reflecting the activity of the 6 beta-hydroxylase) decreased linearly with the metabolic clearance of prednisolone. Despite increased prednisolone exposure, elderly subjects had higher endogenous cortisol concentrations. It was concluded that elderly subjects exhibit higher concentrations of both total and unbound prednisolone. Despite this greater exposure of target tissues, there appears to be less suppression of endogenous cortisol concentrations in plasma compared with younger subjects.