It is clear that corynebacteriorophage beta carries the structural gene for diphtheria toxin. The tox gene is only expressed at maximal levels when lysogenic toxinogenic Corynebacterium diphtheriae becomes iron starved. I have previously shown that the regulation of tox expression is directed at the level of transcription (Murphy et al. 1978), and that iron is likely to act as a co-repressor together with a bacterial determined apo-repressor in the negative control of toxin synthesis. I have proposed the continued study of the molecular biology of diphtheria tox regulation. I have become increasingly interested in the problem of diphtheria toxin eucaryotic cell interactions. Specifically, the nature of the diphtheria toxin eucaryotic cell receptor binding domain, and the mechanism(s) subsequent to binding that lead to the entry of fragment A into the cytosol. I have shown in this proposal that these areas of research are amenable to biochemical genetic analysis and have proposed experiments for the continuation of my study in these fields. The long range objectives of this proposal are to understand the molecular mechanism(s) that are involved in the iron mediated regulation of the beta-phage diphtheria tox gene, as well as to develop the molecular biology and molecular genetics of the tox gene.