The aerial architecture of flowering plants is determined to a large extent by shoot growth and shoot branching arising from the initiation and growth of axillary meristems. We have identified an Arabidopsis mutant, supershoot (sps), which is characterized by a massive overproliferation of shoots, such that a single plant can generate 500 or more inflorescences. Analysis of the mutant plants shows that the primary defect is because of an increase in the number of meristems formed in leaf axils, together with release of bud arrest, resulting in reiterative branch formation from rosette and cauline leaves. The SPS gene is shown here to encode a cytochrome P450, and together with a 3- to 9-fold increase in levels of Z-type cytokinins in sps mutant plants, indicate a role for SPS in modulating hormone levels. The expression pattern of SPS, with strong expression at the leaf axils, correlates well with the phenotypic defects. Our results indicate that control of shoot branching in Arabidopsis may be accomplished in part by suppression of axillary meristem initiation and growth through the localized attenuation of cytokinin levels at sites of bud initiation.