The effects of short-term use of a small dose of dexamethasone on the pharmacokinetics and pharmacodynamics of the CYP3A4 substrate, triazolam, were examined. In a randomized, double-blind cross-over study with two phases, ten healthy volunteers were given either 1.5 mg dexamethasone or placebo once a day for 4 days. On the 5th day, 0.5 mg triazolam was administered orally. Plasma triazolam concentrations and effects of triazolam were measured for 10 hr. Dexamethasone did not have statistically significant effects on the pharmacokinetics of triazolam. The mean total area under the plasma triazolam concentration-time curve was, however, 19% smaller during the dexamethasone phase than during the placebo phase (11.4 +/- 5.7 ng ml-1 hr versus 14.1 +/- 8.8 ng ml-1 hr (mean +/- S.D.); P = 0.09). The four psychomotor tests employed did not show significant differences in the effects of triazolam between the phases. Although dexamethasone had only small effects on the pharmacokinetics and pharmacodynamics of triazolam in the present study, higher doses or prolonged use of dexamethasone might cause a more pronounced induction of CYP3A4. Further studies on the effects of dexamethasone on the pharmacokinetics of CYP3A4 substrates in man are needed.