The aim of this study was to evaluate the ability of diffusion-weighted MRI in differentiating transudative from exudative pleural effusions. Fifty-seven patients with pleural effusion were studied. Diffusion-weighted imaging (DWI) was performed with an echo-planar imaging (EPI) sequence (b values 0, 1000 s/mm(2)) in 52 patients. The apparent diffusion coefficient (ADC) values were reconstructed from three different regions. Subsequently, thoracentesis was performed and the pleural fluid was analyzed. Laboratory results revealed 20 transudative and 32 exudative effusions. Transudates had a mean ADC value of 3.42+/-0.76x10(-3) mm(2)/s. Exudates had a mean ADC value of 3.18+/-1.82x10(-3) mm(2)/s. The optimum cutoff point for ADC values was 3.38x10(-3) mm(2)/s with a sensitivity of 90.6% and specificity of 85%. A significant negative correlation was seen between ADC values and pleural fluid protein, albumin concentrations and lactate dehydrogenase (LDH) measurements (r=-0.69, -0.66, and -0.46, respectively; p<0.01). The positive predictive value, negative predictive value, and diagnostic accuracy of ADC values were determined to be 90.6, 85, and 88.5%, respectively. The application of diffusion gradients to analyze pleural fluid may be an alternative to the thoracentesis. Non-invasive characterization of a pleural effusion by means of DWI with single-shot EPI technique may obviate the need for thoracentesis with its associated patient morbidity.