The fungus Cryptococcus neoformans possesses a polysaccharide capsule and can form biofilms on medical devices. We investigated the efficacy that the combination of a specific antibody to the capsular polysaccharide and antifungal therapy has against cryptococcal biofilms. The antibody enhanced the susceptibility of planktonic cells to antifungal agents, but an antagonistic effect was observed for combination therapy against C. neoformans biofilms. Our findings suggest that antibody therapies for infectious diseases that involve biofilms may antagonize certain antimicrobial therapies, and they also imply that products of the immune response may contribute to drug resistance of biofilms formed in vivo