Objective To examine the role of acute infection as a cause of morbidity in patients with tuberculosis. Design Cross-sectional documentation of predefined acute morbid events. Setting: Infectious Diseases Hospital, Nairobi, Kenya. Patients Adults (≥ 15 years), inpatients and outpatients with a diagnosis of tuberculosis presenting with one or more of a series of clinical features. A new event was defined as one occuring at least 1 week after the initial event. Interventions Patients' treatment was modified depending on the results of laboratory investigations. Main outcome measures There were 642 events from 398 patients, 235 HIV-positive patients had 438 events and 163 HIV-negative patients had 204 events (P< 0.0001). Forty-two out of the 235 (18%) HIV-positive patients were bacteraemic compared with nine out of the 163 (6%) HIV-negative patients (P= 0.0003). The most common isolates from blood were Salmonella typhimurium and Streptococcus pneumoniae. Results Faecal specimens were obtained more commonly from HIV-positive patients (P< 0.001), and often contained bacterial pathogens. Conclusions Many of the causes of morbidity in patients with tuberculosis and HIV are not due to tuberculosis or antituberculous therapy, and will not be identified without microbiological investigation.