The objective of this study was to test the hypothesis that accumulated helper T lymphocytes in malignant pleural effusions may shift to T-helper type 2 (Th2) and produce soluble ST2 protein. We took samples of serum and pleural effusions (p-) from patients with carcinomatous pleurisy (CA, n = 17), tuberculous pleurisy (TB, n = 8), and congestive heart failure (HF, n = 5) and compared the concentration of cytokines or ST2. Ex vivo production of interleukin (IL)-4 and IL-10, though not that of interferon (IFN)-gamma or IL-12, from CD4+ T cells isolated from pleural effusions was higher in the CA group than in the TB or HF group. The p-ST2 concentrations were significantly higher in the CA group than in the TB or HF group, positively correlated with the percentage of pleural effusion CD4+ T cells (r = 0.432, p = 0.016) and inversely correlated with p-IFN-gamma concentrations (r = -0.423, p = 0.019). Furthermore, mRNA expression of ST2 in CD4+ T cells isolated from group CA was upregulated, compared with that in those isolated from the TB group. These results suggest that CD4+ T cells in CA shift to Th2, which can produce soluble ST2 protein, resulting in increased concentrations of p-ST2 in malignant pleural effusion.