The host specificity of Trypanoplasma salmositica was studied by experimental inoculation into 13 species of common teleosts (Notropis cornutus, Notropis heterolepis, Notropis spiloperus, Nocomis biguttatus, Rhinichthys atratulus, Semotilus atromaculatus, Carassius auratus, Ambloplites rupestris, Lepomis gibbosus, Etheostoma nigrum, Hypentelium nigricans, Ictalurus melas, and Eucalia inconstans). T. salmositica was not recovered at 14 and 40 days post inoculation. However, large numbers of the parasite were recovered from Salmo gairdneri and Cottus cognatus, thus indicating that sculpins might be reservoir hosts in certain areas where salmonids and sculpins occur in close proximity. Using a modified In Vitro Plasma Incubation Technique, it was shown that the plasma of refractory fishes had lytic ability and the titer ranged from 1:4 to 1:8. Undiluted fresh plasma of goldfish and of the northern hog sucker lysed about 500 parasites within 30 to 60 mins at 4 C. This lytic ability of fresh plasma was heat labile and partial coagulation of the blood also reduced the lytic titer. This study showed that Trypanoplasma salmositica was more host specific than orginally reported. It was suggested that the mechanism responsible for providing the innate immunity to this parasite in some fishes was the Alternate Pathway of Complement Activation.