The effects of terfenadine, a non-sedating antihistamine, on the pharmacokinetics and pharmacodynamics of buspirone, a CYP3A4 substrate, were investigated in a randomised, placebo-controlled, two-phase cross-over study. Ten healthy volunteers took either 120 mg terfenadine or matched placebo orally once daily for 3 days. On day 3, 10 mg buspirone was taken orally. Plasma concentrations of buspirone were measured up to 18 hr and its pharmacodynamic effects up to 8 hr. Terfenadine slightly but not significantly increased plasma concentrations of buspirone. No psychomotor deterioration was observed during the terfenadine phase. In conclusion, terfenadine did not significantly affect the pharmacokinetics of buspirone, a CYP3A4 substrate shown to be very susceptible to interactions with CYP3A4 inhibitors. Thus, terfenadine is expected to have little effect on the pharmacokinetics of CYP3A4 substrates in general.