The effective use of microsatellite loci as tools for microevolutionary analysis requires knowledge of the factors influencing the rate and pattern of mutation, much of which is derived from indirect inference from population samples. Interspecific variation in microsatellite stability also provides a glimpse into aspects of phylogenetic constancy of mutational processes. Using long-term series of mutation-accumulation lines, we have obtained direct estimates of the spectrum of microsatellite mutations in two model systems: the nematode Caenorhabditis elegans and the microcrustacean Daphnia pulex. Although the scaling of the mutation rate with the number of tandem repeats is highly consistent across distantly related species, including yeast and human, the per-cell-division mutation rate appears to be elevated in multicellular species. Contrary to the expectations under the stepwise mutation model, most microsatellite mutations in C. elegans and D. pulex involve changes of multiple repeat units, with expansions being much more common than contractions.