Clathrin-coated membranes and coated vesicles take part in the selective transfer of proteins between different subcellular compartments of eukaryotic cells. To allow assessment of the role of clathrin in vesicular transport, genetic analysis of the clathrin heavy chain gene (CHCl) in Saccharomyces cerevisiae was initiated. The complete heavy chain gene was cloned, and the effects of deletion of this gene were studied. The null mutation (chcl-.DELTA.) is lethal unless a suppressor of clathrin deficiency (scd1) is present. Even in the presence of the suppressor gene, mutants lacking this clathrin heavy chain grow slowly, are genetically unstable, are morphologically abnormal, and show loss of or reduction in several yeast functions. These results indicate that clathrin is required for normal growth of yeast, and, therefore, most likely, for growth of all eukaryotic cells.