Oral thrush is a common condition in young infants. Nystatin treatment is associated with frequent recurrences and difficulty in administration. Fluconazole was compared with nystatin for the treatment of oral candidiasis in infants. Thirty-four infants were randomized to either nystatin oral suspension four times a day for 10 days or fluconazole suspension 3 mg/kg in a single daily dose for 7 days. Clinical cures for nystatin were 6 of 19 (32%), and those for fluconazole were 15 of 15 (100%), P < 0.0001. In this small pilot study fluconazole was shown to be superior to nystatin suspension for the treatment of oral thrush in otherwise healthy infants.