Lithium ions have long been known to exert dramatic effects on the specification of cell fates in multicellular systems. We have analyzed the effects of Li+ on intracellular patterning in a complex unicellular organism, the ciliate Tetrahymena thermophila. LiCl does not affect the locations of major structural landmarks in the cortical region of wild-type cells and does not modify the phenotype of pattern-mutant cells. However, in all strains studied LiCl differentially affects early stages of oral development. It initially triggers a slow regression of oral primordia, which is followed by an excessive proliferation of basal bodies that leads to a hypertrophy of the ciliature of the cell's feeding organelle. This hypertrophy mimics the effects of the membranellar-pattern-D mutation, the phenotype of which is enhanced in the presence of LiCl. These effects were partially reversed by myo-inositol; however, neomycin failed to mimic the effects of LiCl. Thus, although lithium ions have major cellular effects on Tetrahymena, they do not influence the specification of the body plan in a manner analogous to that observed in multicellular organisms and may work in part through mechanisms other than the now-classical inositol-phosphate cycle.