The effects of levamisole, ribovirin, and cyclophosphamide in preventing the spontaneous autoimmune disease of NZB/W mice have been evaluated. These drugs all had a significant effect, both in delaying mortality, and in postponing the development of antinuclear antibodies and proteinuria. Single-stranded DNA linked to IgG was also used but had no demonstrable effect. The results of therapeutic studies in murine lupus must be interpreted with caution in relation to the human disease, but as both levamisole and ribovirin are now being used in man, our results suggest that further studies with these drugs are warranted.