We previously provided in vitro evidence that the cell surface glycoprotein of Mr80,000 (gp80) of Dictyostelium discoideum is capable of mediating EDTA-resistant cell-cell binding. Expression of gp80 is specific for the aggregation stage when cells form tight aggregates. To investigate the physiological role of gp80, Dictyostelium cells were transformed with a vector containing gp80 cDNA fused to an actin promoter. gp80 transcripts were detected in transformed cells in their vegetative growth phase. Transformants at this stage also exhibited EDTA-resistant cell cohesion, thus providing direct in vivo evidence that gp80 mediates cell-cell binding via homophilic interaction. While aggregates of the parental strain KAX3 had the tendency to break up to form small slugs, transformants expressing an increased amount of gp80 were able to maintain the integrity of aggregates, giving rise to larger slugs, resulting in the formation of bigger fruiting bodies. To further demonstrate that the increase in slug size could be correlated with the expression of gp80, cells of the parental strain were treated with exogenous cAMP pulses to stimulate an over-expression of gp80. The treated cells also gave rise to larger slugs, consistent with the notion that slug size is influenced by intercellular adhesiveness during development.