Pentoxifylline (PTX) is a methylxanthine derivative whose diverse mechanisms of action are now extensively documented. It may play a role in various diseases via a pharmacologic modification of cytokine dysregulation. Despite many encouraging results in animal models, it has not yet been demonstrated that PTX could have beneficial effects in other diseases than intermittent claudication. We selected three clinical conditions that may benefit from PTX and are trying to clarify its potential for use in these disorders. The use of allogeneic bone marrow transplantation is limited by its toxicity, although this form of therapy is able to cure many hematologic malignancies. We are performing a placebo-controlled trial to evaluate the ability of PTX to decrease transplant-related toxicity. In severe chronic respiratory insufficiency, a study is ongoing to compare the number of infectious exacerbations under PTX or placebo. Finally, we have planned a long-term prevention study in patients with peripheral arterial disease. We present here the rationale and design of these trials.