Summary: Three Coxsackie viruses, the DeMole, Wiederhold, and High Point agents, were investigated with regard to their capacity to multiply in suspended cell or roller tube cultures of various human tissues. Marked differences in the in vitro behavior of the three viruses were demonstrated. The Wiederhold virus exhibited a cytopathogenic effect on the cells of both embryonic and mature tissues. In sharp contrast, multiplication of the High Point agent was observed only in cultures prepared with human embryonic brain tissue. Multiplication of the DeMole virus occurred in cultures of embryonic brain and intestine and mature kidney, but not in those of embryonic skin and muscle tissue. Evidence of cytopathogenicity was presented only in cultures of embryonic brain and intestine. This agent also multiplied in cultures of embryonic mouse tissues.