Using clathrin heavy chain (CHC1) mutants of S. cerevisiae, we have previously shown a role for clathrin in retention of resident membrane proteins in the trans-Golgi network (TGN), delivery of proteins to the vacuole, and receptor mediated endocytosis. In order to identify additional proteins involved in clathrin mediated vesicular transport we screened for mutants which display synthetic lethality with a temperature sensitive allele of CHC1 (chc1-ts). A collection of mutants, termed tcs (ts-clathrin synthetic mutant), has been isolated. Included in this collection are mutants which show defects characteristic of chc1 cells such as secretion of a precursor form of *alpha*-factor and/or secretion of the vacuolar hydrolase CPY. Complementation analysis with mutants which show both these defects suggests that mutant alleles of the vacuolar protein sorting mutants VPS1 (dynamin homolog), VPS21 (Rab homolog), and VPS6 (PEP12; syntaxin homolog) were uncovered in this screen. These findings underscore the importance of vesicular transport between the TGN and a prevacuolar compartment for clathrin-mediated protein retention. A mutant allele of RIC1 (chromosome XII) was also identified in the screen. RIC1 mutant strains have been previously reported to be defective in the transcription of both ribosomal protein genes and ribosomal RNA. The involvement of RIC1 and other tcs mutants in clathrin-mediated protein trafficking is currently under investigation.