AIMS OF STUDY: to analyse, in contacts exposed to smear+/culture + (S+/C+) or S-/C+ TB, most of whom are foreign-born: 1) correlation between T-SPOT.TB IFN-gamma release assay (Oxford Immunotec, UK), TST and exposure scores; 2) agreement between T-SPOT.TB and TST in Bacillus of Calmette-Guérin (BCG) vaccinated and non-vaccinated subjects, and 3) impact of results of T-SPOT.TB on diagnosis and treatment for latent tuberculosis infection (LTBI). PATIENTS AND METHODS: TST and T-SPOT.TB were performed in 295 contacts (74% foreign-born) 8-12 weeks after exposure. Contacts completed five exposure scores. Data were analysed according to most recent US (ATS/CDC), British (NICE) and Swiss guidelines. RESULTS: T-SPOT.TB was positive in 115 (39%) and indeterminate in 15 subjects (5.1%). Neither TST, nor T-SPOT.TB was significantly related to exposure scores or infectiousness of the index case. In multivariate analysis, incidence of TB in country of origin was the strongest predictor of result of TST or T-SPOT.TB. Agreement between TST and T-SPOT.TB (kappa: 0.19-0.27) was low but improved in non BCG-vaccinated subjects (kappa: 0.28-0.47). According to guidelines referred to, 10-24% of subjects screened were T-SPOT.TB+/TST-: the prognosis of this group is yet undetermined. Another 10-27% were T-SPOT.TB-/TST+: present guidelines recommend withholding treatment for LTBI in these subjects although longitudinal data are still scarce. CONCLUSIONS: The lack of a relationship between T-SPOT.TB and exposure scores probably results from both the variability inherent to the design of this study (ie, multiple contact investigations, exposure in different settings) and limits in the performance of the IGRA tested. Longitudinal data are needed to clarify the risk of TB in T-SPOT.TB+/TST- individuals. Unreliability of diagnosis of LTBI in spite of the present use of IGRA in algorithms is illustrated by the wide variations in identification of LTBI according to different guidelines referred to.