Pleural effusions can be caused by highly different underlying diseases and are characterized by complex interactions of various local and circulating cells as well as numerous soluble parameters like interleukins (IL). Knowledge about this complex network could help to indicate underlying disease. Therefore, we have investigated immunoreactive concentrations of IL-4, IL-6, IL-11, IL-15, IL-17, IL-18, and tumor necrosis factor-alpha (TNF-alpha) in pleural effusions and peripheral blood from patients with tuberculosis, bronchial carcinoma and other carcinomas as well as congestive heart failure (CHF) and pneumonias. To determine the value of cytokine measurement for differential diagnosis, statistical and fuzzy-logic methods were applied. Quantitative analysis showed high concentrations of IL-6 and IL-11 only in pleural effusions. IL-15, IL-17, IL-18 and TNF-alpha could be detected also in blood plasma. Lowest amounts were detected in CHF indicating the non-inflammatory origin of effusions. Statistical analysis did not provide evidence for diagnostic relevance of singular cytokines. Fuzzy-logic analysis was able to assign patients to the correct diseases with 80% accuracy using IL-6 and IL-15 measurement. Our results confirm the pathogenetic role of these cytokines in pleural effusions. Fuzzy-logic-based procedures may help to characterize and distinguish effusions of unknown origin even in small patient groups.