A placebo-controlled study of immunotherapy with Mycobacterium vaccae for chronic plaque psoriasis showed improvement in the psoriasis area severity index in 19 of 21 immunotherapy recipients (P<0.005). Minor improvement, not reaching statistical significance for the group, occurred in nine of 14 placebo recipients. There were losses to follow-up and the placebo used, tetanus toxoid, was not ideal. Clinical improvement after immunotherapy persisted for 6 months and another injection of the immunotherapeutic given to a few volunteers from either group resulted in benefits lasting a year. Lymphoproliferative tests were carried out at each clinic visit, and on 50 matched controls. Starting with reduced responses to mycobacterial antigens and concanavalin A, both treatment groups showed a fall after 3 months, and diverged at 6 months with M. vaccae recipients rising to values similar to those of healthy controls, whereas placebo recipients continued to fall. Conclusions reached were that immunotherapy with M. vaccae gave long-lasting clinical benefit to most patients, with minimal side effects. This accompanied a return towards normal cellular immune responsiveness to mycobacterial antigens, which did not follow the use of the placebo.