In recent years, biological agents have emerged as the most popular drugs for the treatment of rheumatoid arthritis (RA). The most frightening side effects of biological agents are infections, with tuberculosis being the leader. On account of the fact that biological agents have been used widespread, a number of algorithms have been developed to search latent tuberculosis. Among these algorithms, the most popular is the purified protein derivatives (PPD) test which is based upon late sensitivity reaction. The objective of this trial is to investigate the relevance of PPD response for the disease in RA patients. A total of 149 subjects (80 patients, 69 healthy), 35 RA patients who have not been treated before, 23 RA and 22 AS patients who are candidates for biological agents and being treated with immunosuppressive drugs, and 69 healthy subjects, have been included in this trial. Swelling joints, number of tender joints, visual analog scale, erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor were recorded. PPD was performed using the Mantoux method and was measured 72 h later. Statistically significant lower PPD values were determined in untreated RA patients compared to PPD values of treated RA and AS patients and healthy subjects. No correlation was determined between disease activity score 28 activity and PPD values in untreated and treated groups. Similarly, there was no correlation between acute phase reactants and PPD. Lower PPD responses in patients not being treated with immunosuppressive are due to the disease itself, rather than to the drugs being used. It is also important to interpret PPD results in early RA patients with suspicion, when it is intended to start anti tumor necrosis factor therapy.