The protein products of Polycomb group (PcG) and trithorax group (trxG) genes are required for the maintenance of the transcriptionally repressed and active states, respectively, of the homeotic genes. Mutations in PcG genes produce gain-of-function (posterior) homeotic transformations, while mutations in trxG genes produce loss-of-function (anterior) homeotic transformations. Double mutant combinations between a PcG gene and a trxG gene suppress the homeotic transformations seen with either mutation alone, suggesting that PcG and trxG genes act antagonistically. The PcG gene Additional sex combs (Asx) is interesting because one mutant allele, AsxP1, causes both anterior and posterior homeotic transformations. AsxP1 and other Asx mutations were crossed to mutations in the PcG gene Polycomb (Pc) and the trxG gene trithorax (trx). Asx alleles enhance both PcG and trxG homeotic transformations, showing that Asx is required for both the activation and the repression of homeotic loci. Asx also shows strong allele-specific interactions with the PcG genes Pc and super sex combs (sxc). Together, these data indicate that there are functional interactions between Asx, Pc and sxc in vivo. ASX may interact with a PcG complex containing PC and SXC and mediate activation versus repression at target loci, perhaps by interacting directly with the TRX protein.