MUTATIONS are a double-edged sword : they are the ultimate source of genetic variation upon which evolution depends, yet most mutations affecting fitness (viability and reproductive success) appear to be harmful(1). Deleterious mutations of small effect can escape natural selection, and should accumulate in small populations(2-4). Reduced fitness from deleterious-mutation accumulation may be important in the evolution of sex(5-7), mate choice(8,9), and diploid life-cycles(10), and in the extinction of small populations(11,12). Few empirical data exist, however. Minimum estimates of the genomic deleterious-mutation rate for viability in Drosophila melanogaster are surprisingly high(1,13,14), leading to the conjecture that the rate for total fitness could exceed 1.0 mutation per individual per generation(5,6). Here we use Escherichia coli to provide an estimate of the genomic deleterious-mutation rate for total fitness in a microbe. We estimate that the per-microbe rate of deleterious mutations is in excess of 0.0002.