Malignant ascites formation is a grave prognostic sign, but palliative efforts seem justified in some patients. Lack of knowledge concerning the natural history of this process hinders the choice of therapeutic options. Over 5 years, 107 patients with untreated malignant ascites were reviewed to define their survival. Pancreas (20), ovary (18), and colon (18) were the most frequent tumors, with 52% of patients presenting with ascites at the time of the initial cancer diagnosis. Cytology evaluation of the ascitic fluid was positive for tumor cells in 57% of cases and a high protein content was noted in 65%. Mean survival of the entire series was only 20 weeks from the time of diagnosis of ascites, with tumors of ovarian and lymphatic origin having better mean survivals of 32 and 58 weeks, respectively. Patients with high ascitic protein levels fared better than those with low levels. In an effort to explain this correlation of elevated protein levels and a favorable survival rate, a hypothesis was proposed that certain tumors secrete a factor, which alters vascular permeability and causes fluid accumulation in the absence of lymphatic obstruction. In an experimental rat model of malignant ascites, the intraperitoneal infusion of cell-free malignant ascitic fluid caused an increase in edema formation and a significant increase in capillary permeability to protein in the omentum. This demonstrated change in the leak of protein explains the formation of ascites by some tumors in the absence of tumor obstruction of the draining lymphatics of the peritoneal cavity and suggests another important mechanism in the genesis of malignant ascites.