In the leafy mutant of Arabidopsis, most of the lateral meristems that are fated to develop as flowers in a wild-type plant develop as inflorescence branches, whereas a few develop as abnormal flowers consisting of whorls of sepals and carpels. We have isolated several new alleles of leafy and constructed a series of double mutants with leafy and other homeotic mutants affecting floral development to determine how these genes interact to specify the developmental fate of lateral meristems. We found that leafy is completely epistatic to pistillata and interacts additively with agamous in early floral whorls, whereas in later whorls leafy is epistatic to agamous. Double mutants with leafy and either apetala1 or apetala2 showed a complete loss of the whorled phyllotaxy, shortened internodes, and suppression of axillary buds typical of flowers. Our results suggest that the products of LEAFY, APETALA1, and APETALA2 together control the differentiation of lateral meristems as flowers rather than as inflorescence branches.