The laboratory BS-90 strain of the freshwater pulmonate snail Biomphalaria glabrata, progeny of snails collected from Salvador, Brazil, is resistant to infection with Schistosoma mansoni as juveniles or adults, which rapidly kill primary sporocysts with an attack by the internal defense system (IDS). However, neonatal snails are susceptible to infection. Although neonatal susceptibility of Salvador B. glabrata was reported in 1953 and confirmed subsequently, this phenomenon has been largely ignored. In this study, susceptibility was examined in discrete sizes (shell diameters) of BS-90 snails. We found that 1-mm snails are highly susceptible and develop patent infections. Unexpectedly, most infected 1-mm snails contain primary sporocysts in the digestive gland. Snails measuring 2 and 3 mm show a reduced prevalence of infection, and 4-mm and larger snails are refractory. In snails larger than 1 mm, sporocysts fail to develop normally, as shown by reduced numbers of germinal cells 48 hr post-exposure. Moreover, in larger snails an increasingly stronger response of the IDS is mounted in the form of increased numbers of sporocysts undergoing encapsulation and destruction by hemocytes, and increased layers of encapsulating hemocytes, as well as increased mitotic activity of the hematopoietic amebocyte-producing organ. These results indicate a relatively narrow size range over which resistance develops and suggest that the IDS of 1-mm snails is developmentally immature. The occurrence of infections in neonatal snails may help to explain the transmission of schistosomiasis in regions of low snail susceptibility and may complicate future efforts in biological control.