A variety of innate defense factors in saliva such as lysozyme and lactoferrin contribute to mucosal protection and modulate Candida populations in the oral cavity. It is also known that in human immunodeficiency virus (HIV)-infected individuals significant variations in the concentrations of lysozyme and lactoferrin in saliva occur during disease progression. Therefore, the aim of this study was to determine the in vitro susceptibility to human lactoferrin and hen egg white lysozyme of genotypically similar oral Candida albicans isolates obtained from six HIV-infected ethnic Chinese during sequential visits over a 12-month period. The similarity of the genotypes (50 in total) was evaluated using a randomly amplified polymorphic DNA assay. A blastospore viability assay was performed to evaluate the sensitivity of the organisms to lysozyme and lactoferrin. Exposure to physiological concentrations of either lysozyme (30 g/ml) or lactoferrin (20 g/ml) caused a rapid loss of viability among all isolates to a varying extent. None of the sequential C. albicans isolates demonstrated significant differences in sensitivity to either protein from one visit to the next; similar results were noted when the different genotypes from the same individual were compared. On Spearman correlation analysis of two genotypes that were sequentially isolated from a single patient, a significant negative correlation between lysozyme (r ؍ ؊0.88; P < 0.02) (but not lactoferrin) resistance and the duration of HIV disease was seen. These results imply that a minority of C. albicans isolates that persist intraorally in individuals with HIV disease develop progressive resistance to innate salivary antifungal defenses such as lysozyme, possibly as an adaptive response. However, the vast majority of the Candida isolates appear to succumb to these nonspecific host immune mediators abundantly present in the oral environment.Candida albicans is the main cause of oral candidiasis in patients with human immunodeficiency virus (HIV) infection and AIDS (13, 38). Almost 90% of AIDS patients suffer from oropharyngeal or esophageal candidiasis at some stage of their disease (38). As HIV infection progresses, so does the oral colonization by Candida, and it eventually becomes a permanent oral resident despite prophylactic antifungal therapy (1,36,45). With the development of DNA fingerprinting methods, it is now possible to investigate strain relatedness and emergence of novel strains of C. albicans by sequentially sampling a cohort of individuals either with or without symptomatic oral candidiasis. Several authors have shown that AIDS patients are frequently infected with the same C. albicans strains over recurrent episodes of oral thrush (5, 34, 47, 60), and others have found, for instance in Candida vaginitis, that the same yeast strain may persist through successive episodes of infection (48,49). Although these and other studies have traced the yeast genotypes over multiple infection episodes (29,36,45), not many have investigated the phenotypic attr...