Abstract: Anti-idiotypes (anti-Ids) have a potential role in the immune modulation of various diseases. To study the correlation of anti-Ids with schistosomiasis mansoni morbidity, ELISA using polyclonal idiotypes (Ids) was used to determine the presence of anti-Ids in sera of 69 patients susceptible and resistant to re-infection. Ids were purified against Soluble Worm Antigen (SWAP) from sera of New Zealand white rabbits immunized with SWAP. The results showed that anti-Ids were detected in 15 (40.5%) of susceptible and 21 (65.6%) of resistant patients. Correlation of intensity of infection with age revealed an inverse relationship in patients positive for anti-Ids (regression coefficient β = - 0.47, p<0.05) and contrarily, a direct relationship in patients negative for anti-Ids (β = 0.67, p<0.001). In addition, there was a direct association between the presence of anti-Ids and the lack of schistosome-related symptoms (χ2 = 3.6, p<0.05) and hepatomegaly (χ2 = 9.4, p<0.01). Moreover, comparison of patients positive and negative for anti-Ids revealed that those negative for anti-Ids were more vulnerable to develop symptoms (3.7 times) and hepatomegaly (8.1 times). In conclusion, the study further confirms the role of Id/anti-Id regulatory network as an important participant in the assortment of an improved clinical outcome of schistosomiasis. This may help to formulate a better understanding of the mechanisms of protective immunity in humans and provide perspective for the development of a future vaccine.