Recent data indicate that cortical dopamine denervation results in dystrophic changes in the dendrites of pyramidal cells, including decreases in dendritic spine density and length. However, it is not known if the loss of signaling through specific dopamine receptors subserves these dendritic changes. We examined the dendritic structure of layer V pyramidal cells in the prefrontal cortex of D(1), D(2), and D(4) dopamine receptor null mutant mice and their wild-type littermates. Decreased basal dendritic length and spine density were observed in the D(1) knockout mice. Similarly, a decrease in basal dendritic spine density was uncovered in the D(2) knockout mice relative to wild-type littermates. No changes in any dendritic parameter were observed in the D(4) knockout mice. These observations suggest that the dystrophic changes observed in prefrontal cortical pyramidal cell dendrites are due to loss of signaling through D(1) and possibly D(2) receptors. The current data also suggest that caution should be exercised in the interpretation of behavioral, physiological, and biochemical studies of the prefrontal cortex in dopamine receptor knockout mice.