The heterochronic genes of C. elegans are global temporal regulators that specify the proper timing and sequence of post-embryonic developmental events. In hypodermal cells, heterochronic genes program stage-specific temporal identities, ultimately triggering expression of adult fates during the final (L4) molt, characterized by seam cell fusion and adult cuticle synthesis. Mutations in these genes advance or retard the timing of the adult seam cell program. For example, hbl-1 mutations cause the adult program to occur one stage early, during the L3 molt. Included among the heterochronic genes are the first two miRNA-encoding genes discovered, lin-4 and let-7. We show that lin-58 is a third genetically defined heterochronic gene that encodes a miRNA. let-7 expression begins in the late L3 and down-regulates target genes allowing stage-specific programs to advance. hbl-1 appears to be a let-7 target; however, misregulation of hbl-1::gfp in let-7 mutants is less than one might expect if let-7 acts alone, suggesting that other gene products function redundantly with let-7 to time hbl-1 expression. Indeed, extensive analysis of worm miRNAs identified three let-7 homologs that have the same temporal expression pattern as let-7. Conceivably, some or all of these miRNAs could participate in hbl-1 regulation through overlapping and/or independent sets of binding sites in the hbl-1 3'UTR. Two let-7 homologs, mir-48 and mir-241, reside in tandem on chromosome V in the interval where lin-58, a heterochronic gene identified as a lin-4 suppressor, maps. To test whether one of these miRNAs is lin-58, we sequenced in the region of the microRNAs. Each lin-58 allele contained a single, independent, point mutation in an inverted repeat in the 1.7 kb region between the miRNAs (~200 bp 5' to mir-48), suggesting they are gene regulatory mutations. Consistent with this idea, the precocious hypodermal phenotype of lin-58(ve33) is weakly dominant, and miR-48 accumulates prematurely in lin-58 mutants. In addition, a precocious phenotype is observed in animals which presumably over express miR-48 due to multiple copies of mir-48(+) on an extrachromosomal array. A 1.0 kb DNA fragment upstream of mir-48 drives GFP expression in seam cells, and enhanced expression is seen when the promoter fragment contains the ve33 lesion. These experiments indicate that lin-58/mir-48 acts in the heterochronic pathway. One possibility is that the lin-58 mutations disrupt a repressor binding site thereby allowing premature miR-48 expression and precocious inactivation of target genes, perhaps including hbl-1.