We have demonstrated that Candida albicans in its hyphal form (H-Candida) acts as a stimulating agent in the cloned macrophage population ANA-1. Both tumor necrosis factor (TNF) mRNA levels and secreted biological activity augment in ANA-1 macrophages exposed to H-Candida. Such effects are observed at an effector-to-target cell ratio of 1:1 and occur after 1 and 3 hr of coincubation, respectively. The phenomenon is independent of the metabolic status of the fungus, since viable as well as heat-killed H-Candida are comparable in inducing TNF mRNA levels. The extent and kinetics of H-Candida-mediated effects are similar to those observed following exposure of ANA-1 macrophages to lipopolysaccharide (LPS). This implies that C. albicans in its hyphal form is a potent macrophage modulator; whether it acts through the same mechanism(s) as LPS remains to be elucidated.