1,10-phenanthroline and its non-chelating isomer, 1,7-phenanthroline were used to inhibit the replication of vaccinia virus (VV). Serial passage of VV in the presence of various concentrations of either 1,10-phenanthroline or 1,7-phenanthroline was carried out. No drug resistant mutants were isolated, suggesting that the observed inhibition was due to a cellular protease as opposed to the putative viral protease G1L. Cultures infected in the presence of the inhibitors, were radio labeled with �����S-methionine at various time points post infection, to determine which step of VV replication was inhibited. Infections in the presence of 1,10-phenanthroline proceeded only through early gene transcription, suggesting that the point of inhibition was uncoating. Finally, cells infected with VV with or without the inhibitors at time zero and eight hours post infection were used to generate transmission electron microscopic images. Taken together these results indicate that inhibition was occurring at the level of uncoating. / Graduation date: 1999