Summary Microdrops were used to isolate interferon treated mouse L cells infected with mengovirus. Three parameters were measured, (1) the time of virus yield, (2) the yield/cell, and (3) the percentage of yielding cells. More than 97% of the control single cells yielded an average of 167 p.f.u./cell with most of them yielding between 11 and 14 h post-infection. Cells treated with interferon yielded later than controls (if at all), and all could be protected to some degree. In both treated and control cells, virus was released over a period of about 15 min. Increasing the multiplicity of infection of challenge virus reduced the effectiveness of a given interferon dose, while increasing the concentration of interferon increased the length of the latent period, decreased the size of the yield, and decreased the number of yielding cells. On the basis of these observations it is proposed that (1) the direct effect of interferon protection is to delay a critical step in virus synthesis, (2) the reduction in yield size and in the number of yielders is due to a progressive loss of the inherent ability of the cell to produce virus, and (3) the delay is the result of interferon, or a molecule induced by it, acting as a competitive inhibitor of some cellular or virus product, needed for the completion of virus synthesis.