The effect of erythromycin on the pharmacokinetics of triazolam was studied in 16 normal male volunteers. Triazolam in 0.5-mg doses was administered alone and after 3 days of receiving erythromycin (333 mg tid) in a randomized complete crossover design. Plasma samples were collected for 24 hours post doses and analyzed for triazolam by electron-capture gas chromatography. Erythromycin administration resulted in a 52% decrease in triazolam clearance, significantly higher triazolam concentrations at the majority of sampling times, significantly longer triazolam half-lives of elimination (5.9 vs. 3.6 hours), and a 30% decrease in the triazolam apparent volume of distribution. No differences were observed in the times of peak triazolam concentration occurrence. In accordance with previously reported drug interactions involving macrolide antibiotics, erythromycin appears to significantly inhibit the metabolism of triazolam.