Pseudoplasmodia of developing Dictyostelium are organized with anteroposterior polarity. We have isolated CAR4, the gene for a new cell-surface, G protein-linked cAMP receptor. CAR4 mRNA is initially expressed during tip elongation and continues to accumulate into culmination. CAR4 is maximally expressed in pseudoplasmodia anteriors which are centers for extracellular cAMP signaling and for organization of cellular patterning. Although car4 null cells progress unperturbed through early development, they exhibit major patterning aberrations as the anteroposterior axis becomes established. Prestalk gene expression is significantly reduced in car4 nulls, whereas prespore-specific markers are overexpressed and detected in zones normally restricted to prestalk cells. Patterning defects are similarly apparent in terminally differentiated fruiting bodies. Our results show that cAMP signaling is required for pattern formation and cellular differentiation during late Dictyostelium development.