Animal models are indispensable tools for understanding physiological and pathological processes, as well as for developing new therapies. Ultimately, the results of animal experimentation must provide information that can guide the development of therapeutic approaches in humans. Significant differences have been reported comparing a gene therapy approach between different animal models. However, little information exists describing differences among the available large animal models. Here we evaluated, in the hemopoietic cells of baboons, a system of selection that has previously demonstrated activity in mice, in dogs, and in human cells ex vivo. This system employs a derivative of the murine thrombopoietin receptor (F36Vmpl), which is conditionally activated in the presence of a small-molecule drug called a chemical inducer of dimerization (CID). Whereas cultured mouse, human, and, to a lesser extent, dog hemopoietic cells all proliferate in response to the F36Vmpl signal, we observed only a minor and variable response to the F36Vmpl signal in the cultured cells of baboons. Similarly, we have noted significant rises in the frequency of transduced hemopoietic cells in mice and in dogs upon CID administration in vivo; however, here we show that responses to CID administration in three baboons were modest and variable. These findings have general implications for the evaluation and development of new strategies for gene therapy.