Trilostane and epostane are synthetic steroids which inhibit the 3beta-hydroxysteroid dehydrogenase enzyme. This enzyme is part of a system which catalyses an essential step in the synthesis of biologically active steroids. In animals and man trilostane preferentially inhibits adrenal steroid synthesis whilst epostane inhibits placental/ovarian steroid synthesis. The synthesis of radiolabelled trilostane and epostane are described. Stability investigations showed these radiolabelled compounds to be susceptible to degradation, although trilostane less so than epostane. Careful handling procedures were essential for metabolism studies. Animal studies showed no difference in the overall excretion and distribution of radioactivity for [[14]Cl-trilostane and [[14]C]-epostane. However the site specific localisation of active components within adrenals and ovaries reflected the in vivo organ selectivity observed for these compounds. In man a major plasma metabolite of trilostane was shown to be 17-ketotrilostane which is intrinsically twice as active as parent compound with regard to 3beta-hydroxysteroid dehydrogenase inhibition. A specific, sensitive and accurate HPLC assay was developed which enabled the measurement of trilostane and 17-ketotrilostane in plasma. Plasma concentrations of 17-ketotrilostane in male volunteers were approximately three-fold higher than trilostane, and consequently this metabolite may be an important contributor to the clinical efficacy of this drug. Micronisation of both trilostane and epostane was shown to be appropriate in order to maximise the oral systemic availability of these compounds. However even with micronised formulations considerable inter-and intra-subject variability was noted. For trilostane, variability in absorption, coupled with individual differences in the metabolism to the more active 17-ketotrilostane, may in part account for the variable efficacy encountered in clinical trials.