To describe features of reactive haemophagocytic syndrome (RHS) in HIV-1-infected adult patients. To compare characteristics of patients with malignancy-associated RHS and infection-associated RHS. Retrospective study in three departments of Infectious Diseases/Internal Medicine at three French tertiary centres. Medical charts of HIV-1-infected adult patients and RHS seen between January 2006 and December 2007 were reviewed. Demographic, clinical and laboratory data obtained at the time of RHS episode were compared between patients with malignancy-associated RHS and infection-associated RHS using non-parametric tests. The overall survival was assessed using the Kaplan-Meier method. Fifty-eight HIV-1-infected patients were diagnosed with RHS certain RHS n = 43, possible RHS n = 15, median (range) age 42 (23-85) years, men 76%. At time of RHS, the median duration of HIV infection was 4 (0-22) years and 57% received HAART. The median CD4 lymphocyte count was 91 (2-387)/microl and 35% of patients had a plasma HIV-1 RNA less than 50 copies/ml. Underlying haemopathy/malignancy (Hodgkin lymphoma n = 10) or infection (tuberculosis n = 9, cytomegalovirus infection n = 5) were evidenced for 31 and 23 patients, respectively. Patients with haemopathy/malignancy-associated RHS presented more frequently with splenomegaly (97 vs. 70%, P < 0.01), lower aspartate aminotransferase (36 vs. 84 UI/l, P < 0.01) and lactate dehydrogenase (530 vs. 911 UI/l, P < 0.01) levels and CD8 cell count (234 vs. 588/microl, P < 0.01). Eighteen (31%) patients died. The overall survival was not statistically different between the two groups (P = 0.68). In the HAART era, RHS is frequently associated with underlying haemopathy/malignancy, especially Hodgkin lymphoma. The prognosis remains poor but seems, however, better than in the pre-HAART era.