The in vitro interaction of pentamidine with ketoconazole and with itraconazole was studied with 10 strains of Candida albicans isolated from acquired immunodeficiency syndrome patients and one azole-resistant strain. Although growth curves indicated that concentrations of 1 microgram or more of pentamidine per ml significantly inhibited the growth of C. albicans, MICs and minimum fungicidal concentrations (MFCs) were greater than or equal to 10 micrograms/ml. Combinations of ketoconazole and pentamidine did not appear to have any significant effect on MICs or MFCs with most strains. However, the azole-resistant strain exhibited a 2-log decrease in MIC when exposed to ketoconazole combined with 1.0 microgram or more of pentamidine per ml. Similar results were obtained with itraconazole. An Eagle, or paradoxical, effect was observed with four strains exposed to itraconazole alone and in combination with 0.01 and 0.1 microgram of pentamidine per ml. This effect was not seen when concentrations of pentamidine reached 1.0 microgram/ml. Although no fungicidal effect was observed with any of these drugs alone, itraconazole combined with 10 micrograms of pentamidine per ml was fungicidal for eight strains. No signs of antagonism between pentamidine and these two antifungal agents were observed.