Candida species are usually commensal organisms, but they become invasive when the host is immunocompromised. Mechanisms by which these organisms adhere to, colonize, and then invade host tissues are poorly understood. To detect potential host receptors, members of a lipid library were chromatographically separated and then overlaid with Candida tropicalis; components to which the organisms bound were visualized by autoradiography. In initial experiments no interactions with either glycolipids or intact phospholipids were detected. However, lysophospholipids supported adherence of C. tropicalis but not Saccharomyces cerevisiae. These results were confirmed by a second assay; C. tropicalis adhered to certain lysophospholipids, but not intact phospholipids, that were immobilized on microtiter plates. Using [14C]-1-palmitoyl-sn-glycero-3-phosphocholine, we showed that C. tropicalis adherence is accompanied by rapid conversion of the labeled lipid to a number of compounds. Thus, the interaction of C. tropicalis with lysophospholipids results in significant changes in both the organism and the lysophospholipid to which it binds. We hypothesize that this interaction could be an important component of the infection process.