FUS1 encodes a surface-localized protein known to be important for cell fusion during S. cerevisiae conjugation. We find that mutations in FUS1 cause a subtle mating defect when introduced into a wild-type background, but result in an exaggerated mating defect when introduced into cells deleted for SST2. To identify new genes involved in cell fusion, we carried out a screen for mutations that lead to synthetic sterility when combined with an sst2 deletion. In addition to FUS1, this screen isolated mutations in FUS2, FUS3, RVS161, SPA2, CHS5 and BNI1. We find that mutations in each of these genes cause cell fusion defects, resulting in the accumulation of prezygotes, during both unilateral and bilateral mating reactions. We suggest that these genes promote a common function during cell fusion, because the overexpression of FUS1 and FUS2 suppress the mating defect associated with all of the synthetic sterile mutants. spa2 and bni1 mutants also display a defect in projection formation following exposure to pheromone. Thus, there may be a functional relationship between the components that promote cell fusion and those which participate in polarized growth. We are further characterizing the role of BNI1 in these processes.