The antitumour efficacy of lipid A mutant Salmonella was evaluated alone and in combination with X-rays in mice bearing B16F10 or Cloudman S91 melanomas. Each treatment alone slowed tumour growth and prolonged survival, and the combined treatments produced supra-additive antitumour effects. That is, in dose-response studies with single doses of Salmonella and increasing doses of radiation, the two agents together caused suppression of tumour growth that was greater than that calculated for additivity. The results suggest that the combination of these genetically engineered Salmonella with radiotherapy could be a new and beneficial treatment for solid tumours.