The development of resistance of outbred white mice to two plaque size variants of Sindbis virus was studied as a function of host age. A sudden drop in mortality occurred over a 3-day period. As little as 1 plaque-forming unit (PFU) per mouse was lethal in 1-day-old animals, whereas inocula of 109 PFU per mouse failed to produce high mortality in weanlings. A comparison of viral growth kinetics shows that early replication was similar in newborns and weanlings but that after 6 to 8 hr the production rate and, therefore, the maximal viral titer were suppressed in weanlings. The data demonstrate a lethal viral threshold. Titers in excess of this level lead to mortality, whereas those below it allow survival.