Cell surface cAMP receptors (cARs) have been implicated in multiple aspects of development in Dictyostelium. Antisense mutagenesis has recently provided strong evidence that cARs are necessary for aggregation (Klein et al., 1988. Science (Wash. DC). 241:1467-1472). We show here that the expression of cAR1 antisense mRNA which prevents the appearance of cAR1 antigen also prevents the expression of cAMP-binding activity and blocks multiple cAMP-mediated responses. Chemotactic sensitivity to cAMP was lost as were stimulus-induced cAMP and cGMP production. Furthermore, the expression of developmentally regulated marker genes, dependent on repeated cAMP stimulation, was altered. As a result, the developmental program was severely impaired; most of the cells failed to aggregate and undergo further differentiation.