Between June 1989 and December 2005, an observational study of adults co-infected with HIV and Trypanosoma cruzi was conducted, to investigate the spectrum of manifestations of chronic Chagas disease (American trypanosomiasis) in the HIV-positive. The 31 men and 22 women investigated were aged 23-59 years. Each subject was investigated by ambulatory (Holter) and non-ambulatory electrocardiography, chest X-ray, oesophagography and echocardiography (to determine the clinical form of trypanosomiasis), by xenodiagnosis, blood culture and the microscopical examination of blood (to explore their T. cruzi parasitaemia), and by counting their CD4 T cells (to stage their HIV infection). The subjects were followed-up for 1-190 months (median = 58 months) and checked for re-activation of their Chagas disease, which was usually defined by the occurrence of unusual clinical manifestations and/or the detection, by microscopical examination, of trypanosomes in the blood or cerebrospinal fluid. Eleven (20.8%) of the subjects showed re-activation, another nine (17.0%) were found to have developed high T. cruzi parasitaemias but these were only detected by xenodiagnosis or culture, and 15 (28.3%) had illnesses typical of chronic Chagas disease in HIV-negative individuals, with low parasitaemias. Anti-T. cruzi therapy (benznidazole), recommended for 17 patients, resulted in the sustained reduction of parasitaemia in 11 of the 12 subjects who completed treatment. Chagas disease was the cause of death of eight of the 14 subjects who died during the study. Four of the women investigated gave birth, each to a single child, during follow-up, and three of the four babies showed evidence of the congenital transmission of T. cruzi.