With the dawn of the post-genomic era and the impact of the genomic revolution, knowledge of most of the encoded genes and their molecular nature has been revealed. However, knowledge of the in vivo functions for most of the genes remains incomplete. Thus, the study of phenotypes, or phenomics, has emerged as a genome-wide discipline to link gene sequence and function. Zebrafish has become an attractive and accessible vertebrate model system for phenomics, providing new insights into genotype-phenotype relationships and for modeling human disease. The Sanger Center has developed a high-throughput mutation identification approach to generate a large set of molecularly-defined mutant genes in the zebrafish. It has focused its phenotypic analysis on the embryonic to early larval period and has found that most null mutant alleles do not exhibit an apparent function during these early developmental stages. We have established a new phenotyping screen strategy to identify genes regulating later developmental periods and that act in the adult, as well as to identify human disease genes that typically manifest in the adult. We have analyzed more than 500 molecularly-defined gene knockouts in the zebrafish during late larval to adult stages. We have isolated numerous factors regulating post-embryonic stages, including male sterile, maternal-effect, late larval lethal and adult morphology genes, corresponding to several human disease genes. Our screen serves as the first step towards gaining mechanistic insights into the general structure of complex traits during post-embryonic developmental stages in vertebrates. Importantly, it will contribute to determining the zebrafish phenome during late larval, juvenile, and adult stages, including a collection of traits dispensable for reproduction, survival and body formation. Our studies provide a resource of phenomics data for future in-depth analysis of gene function by the scientific community.