To assess the risk of development of spontaneous bacterial peritonitis in relation to ascitic fluid opsonic activity, routine admission abdominal paracentesis was performed on 119 patients during 141 hospitalizations. Paracentesis was repeated if evidence of peritonitis developed during the hospitalization. The ascitic fluid opsonic activity (0.2 ± 0.5 log kill) of 24 spontaneously infected specimens was significantly (p < 0.001) lower than that of the group with sterile portal hypertension-related ascites (0.8 ± 1.1 log kill), and significantly lower than the group with ascites of miscellaneous type (2.4 ± 1.0 log kill, p < 0.001). The C3 and C4 concentrations of the spontaneous peritonitis specimens were also significantly lower than in the specimens from the other groups. Of the 55 patients whose initial sterile ascitic fluid opsonic activity was <0.2 log kill, 8 (14.5%) developed spontaneous bacterial peritonitis during the hospitalization; whereas none of the 70 patients with sterile ascitic fluid opsonic activity ≥0.2 log kill developed spontaneous peritonitis. This difference in the risk of development of peritonitis was significant (p < 0.01). Patients with deficient ascitic fluid opsonic activity are predisposed to spontaneous bacterial peritonitis.