Two spontaneous cerulenin-resistant mutants of Candida albicans, 4918-2 and 4918-10, were unable to adhere in vitro in fibrin-platelet clots. Because in vitro adherence correlates well with colonization of nonbacterial thrombotic endocarditis on traumatized valvular endocardium, 50% infectious dose studies were performed with a rabbit model of endocarditis. Wild-type C. albicans required 10(3.6) +/- 0.12 cfu in comparison with 10(5.73) +/- 0.31 and 10(7.3) +/- 0.21 cfu for mutants 4918-2 and 4918-10, respectively. The relative avirulence of mutant strains in producing endocarditis was not attributed to accelerated clearance of these strains from the bloodstream. In fact, clearance of wild-type and mutant strains was almost identical. In the same animals renal candidiasis was observed with all strains of C. albicans, although the number of cfu per gram of kidney was higher after infection with wild-type C. albicans. Thus, strains of C. albicans with reduced ability to adhere in vitro to a fibrin-platelet matrix are relatively avirulent in the rabbit endocarditis model.