The use of mutants and molecular genetics has begun to reveal how differentiation is brought about in multicellular, mycelial Streptomyces spp. Alternative pathways to aerial mycelium formation may be activated on different media. In some cases, extracellular signals are transmitted or exchanged. Extracellular proteins may act as morphogens in the erection of aerial hyphae. A rare codon, UUA, is apparently confined to mRNAs from a few genes important only for early stages of differentiation; it is absent from vegetative or developmentally late mRNAs. Sporulation of aerial hyphae involves at least four specific regulatory proteins, including a sigma factor and an unusual small protein. A complex interplay between the sporulation regulatory genes, rather than a simple linear dependence cascade, is emerging.