Background Trifluoperazine, a potent calmodulin inhibitor, is used as an antipsychotic drug. Similar agents have inhibited the growth of yeasts.Methods Susceptibility of 101 Candida albicans strains from patients were tested against trifluoperazine (Trif), ketoconazole (Ktz), and the combination of Ktz with Trif, using Sabouraud's broth.Results The minimal inhibitory concentrations (MlC)s for 101 strains of C albicans were: Trif 65.8±2.1 /xg/ml, Ktz 27.9 ± 9.1 /xg/ml. The combination of Ktz and Trif in various ratios (1:1, 1:2. 2:1) was found to exert synergistic effect and the mean values of the combinations were: Ktz ± Trif 2.72 + 0.17, 2.5 ±0.18, 3.43 + 0.21 ixg/m\. These results were significantly different (P< 0.001) when compared with ketoconazole alone.Outcome Our findings indicate that trifluoperazine (calmodulin inhibitor) increased the antifungal activity of Ktz against C. albicans in vitro.