Idiopathic cutaneous ulcers, oesophageal ulcers and severe ulcerative ileocolitis occurred in a human immunodeficiency virus (HIV)-infected patient early after the initiation of combination antiretroviral therapy. This massive inflammatory process led to acute colonic perforation on two occasions. The disease was refractory to standard therapy, but responded successfully to thalidomide. Here, we discuss the potential benefits of thalidomide in refractory inflammatory processes in HIV-infected patients.