Two experiments evaluated the effects of the simple-to-complex and simultaneous training protocols on the formation of academically relevant equivalence classes. The simple-to-complex protocol intersperses derived relations probes with training baseline relations. The simultaneous protocol conducts all training trials and test trials in separate portions of the protocol. In Experiments 1 and 2, participants formed 4 3- and 4-member neuroanatomy classes, respectively. When trained with the simple-to-complex protocol, 100% of participants immediately formed the 3- or 4-member classes. When trained with the simultaneous protocol, the 3- and 4-member classes were formed immediately by 75% and 42% of participants, respectively. Thus, the immediate emergence of equivalence classes was an interactive function of training protocol and class size. The remaining participants eventually formed classes after a few cycles of retraining. The incorporation of these training and testing parameters could optimize the use of equivalence-based instruction for teaching college-level course content.