A glycoprotein, gp138, is implicated in the sexual cell fusion of Dictyostelium discoideum. We previously cloned and sequenced the two genes encoding the gp138 protein, GP138A and GP138B (Fang et al. (1993) Dev. Biol. 156, 201-208). Here, we have constructed a vector producing antisense RNA for the gp138 genes and have transformed the vector into Dictyostelium cells. The transformed cells showed a reduction in the amounts of gp138 mRNA and protein and their sexual cell fusion activity was considerably repressed.