This study evaluates five synthetic peptides derived from four, potentially protective, Taenia saginata oncosphere molecules for the serodiagnosis of T. solium cysticercosis/neurocysticercosis in three distinct Venezuelan endemic regions. The peptides, all of which have been described previously, are designated HP6-3, Ts45W-1, Ts45W-5, Ts45S-10 and TEG-1. In clinically verified and seropositive hospital cases, combining the results of three of the individual peptide-based ELISAs (HP6-3, Ts45W-1 and Ts45W-5) afforded the best balance between sensitivity (85%) and specificity (83.5%), a significant improvement on the 63.6% specificity obtained with the routinely employed T. solium cyst-fluid-based ELISA. Similarly, in the seropositive Venezuelan endemic zone samples, 89.09% of Amerindians, 77.27% of symptomatic rural subjects and 67.83% of non-symptomatic rural subjects were also classed as seropositive by the combined peptide-based ELISAs. The profile of antibody recognition to individual peptides varied between the different groups of samples examined. The relevance of the above findings for the serology and prognosis of T. solium cysticercosis/neurocysticercosis in hospital- and field-based situations is discussed.