Molecular aspects of spermiogenesis can be studied using mouse mutants and spermatids developed in vitro. The azh/ azh mutant is an attractive model system because structural abnormalities in the sperm head and the ectopic position of the manchette are associated with tail bending and looping. Spermatids, developing an axoneme in vitro and capable of cell motility, offer the possibility of the dynamic analysis of tail development. Offspring generated by intracytoplasmic injection of azh/ azh sperm heads into normal mouse oocytes complement the mouse mutant approach. A central question of sperm tail development is the role of the manchette, a transient microtubular structure assembled soon after the organization of the axoneme. The fractionation of intact manchettes by gradient centrifugation has enabled a biochemical analysis of constitutive tubulin isotypes and transiently associated proteins. For example, keratins Sak57, Odf1, and Odf2 are initially stored in the manchette before being sorted to the outer dense fibers and fibrous sheath of the developing spermatid tail. Additional proteins associated with the manchette include two proteases, the 26S proteasome and N-arginine convertase (both sorted to the developing spermatid tail), a spermatid perinuclear RNA binding protein, Spag4, an Odf1-binding protein, and type 4 cAMP-specific phosphodiesterase D. Keratin 9 and δ-tubulin are two proteins found in the perinuclear ring of the manchette, the insertion site of the microtubular mantle. Available data indicate that the manchette is a highly dynamic structure providing microtubular tracks to structural proteins participating in the sperm tail development.