A 69-year-old man who had been taking digoxin for 2.5 years developed an elevated serum concentration of digoxin in association with digoxin toxicity (characterized by nausea and vomiting) 9 days after the addition of itraconazole to his regimen for the treatment of sternal osteomyelitis. Coadministration of itraconazole resulted in a statistically significant increase in the half-life of digoxin that necessitated a reduction of the digoxin dose by almost 60%. We thus recommend that patients receiving itraconazole and digoxin concomitantly have serum levels of digoxin monitored frequently. In addition, these patients should be carefully questioned about nonspecific gastrointestinal symptoms, which may indicate early digoxin toxicity.