The in vitro susceptibility of 16 isolates of Cryptococcus neoformans to three antifungal drugs and lysozyme in combination was determined using an urea broth microdilution method. The antifungal activities of each drug alone against 16 isolates of Cr. neoformans were determined as mean minimal inhibitory concentrations (MICs). MICs of fluconazole, itraconazole and terbinafine were 2.0 micrograms ml-1, 0.004 microgram ml-1 and 0.25 microgram ml-1, respectively. Lysozyme alone inhibited the growth of Cr. neoformans in a dose-dependent manner, although the lysozyme was unable to kill the cells of Cr. neoformans at the highest concentration of 20 micrograms ml-1. The mean MICs of fluconazole, itraconazole and terbinafine in combination with lysozyme were 0.13 microgram ml-1, 0.004 microgram ml-1 and 0.03 microgram ml-1 respectively. The antifungal activity of fluconazole and terbinafine in combination with lysozyme against Cr. neoformans was greatly enhanced compared with that of each drug alone. Itraconazole was unable to enhance the antifungal activity, as it demonstrated higher activity against Cr. neoformans when alone rather than in combination. Lysozyme was confirmed to enhance the antifungal activity of fluconazole and terbinafine in vitro.