An analysis of the effects of spontaneous mutations affecting age-specific mortality was conducted using 29 lines of Drosophila melanogaster that had accumulated spontaneous mutations for 19 generations. Divergence among the lines was used to estimate the mutational variance for weekly mortality rates and the covariance between weekly mortality rates at different ages. Significant mutational variance was observed in both males and females early in life (up to approximately 30 days of age). Mutational variance was not significantly different from zero for mortality rates at older ages. Mutational correlations between ages separated by 1 or 2 wk were generally positive, but they declined monotonically with increasing separation such that mutational effects on early-age mortality were uncorrelated with effects at later ages. Analyses of individual lines revealed several instances of mutation-induced changes in mortality over a limited range of ages. Significant age-specific effects of mutations were identified in early and middle ages, but surprisingly, mortality rates at older ages were essentially unaffected by the accumulation procedure. Our results provide strong evidence for the existence of a class of polygenic mutations that affect mortality rates on an age-specific basis. The patterns of mutational effects measured here relate directly to recently published estimates of standing genetic variance for mortality in Drosophila, and they support mutation accumulation as a viable mechanism for the evolution of senescence.