During Caenorhabditis elegans spermatogenesis, asymmetric partitioning of cellular components principally occurs via ER/Golgi-derived organelles, named fibrous body-membranous organelles. In C. elegans spe-4 mutants, morphogenesis of fibrous body-membranous organelle complexes is defective and spermatogenesis arrests at an unusual cellular stage with four haploid nuclei within a common cytoplasm. The spe-4 encoded integral membrane protein is a diverged member of the presenilin family implicated in early onset Alzheimer's disease. Specific antisera were used to show that SPE-4 resides within the fibrous body-membranous organelles membranes during wild-type spermatogenesis. Several spe-4 recessive mutants were examined for SPE-4 immunoreactivity and a deletion mutant lacks detectable SPE-4 while either of two missense mutants synthesize and localize immunoreactive SPE-4 within their fibrous body-membranous organelles. One of these missense mutations is located within a motif that is common to all presenilins. spe-4 mutants were also examined for other partitioning defects and tubulin was found to accumulate in unusual deposits close to the plasma membrane. These results suggest that wild-type SPE-4 is required for proper localization of macromolecules that are subject to asymmetric partitioning during spermatogenesis.