Lipo-PGE1 is a drug preparation of PGE1 (prostaglandin E1) incorporated in lipid microspheres similar in properties to liposomes. A multicenter, placebo controlled, double blind test of lipo-PGE1 was carried out in patients with severe peripheral vascular disease secondary to diffuse connective tissue disorders. A total of 135 patients received a 90 min intravenous infusion of either 10 micrograms lipo-PGE1 or placebo every day for 4 weeks. A significant improvement was noted in the lipo-PGE1 group compared with the placebo group in the final overall improvement of peripheral vascular disease (p less than 0.001) and in the healing of ulcers (p less than 0.01), whereas, there was no difference in Raynaud's syndrome between the 2 groups. Side effects in the lipo-PGE1 group were few and were no different from controls. These results indicate that lipo-PGE1 at a low dose is beneficial in the treatment of peripheral vascular disease, and that lipid microspheres are useful as a drug delivery system for such purposes.