Natural and synthetic methylxanthines inhibit insect feeding and are pesticidal at concentrations known to occur in plants. These effects are due primarily to inhibition of phosphodiesterase activity and to an increase in intracellular cyclic adenosine monophosphate. At lower concentrations, methylxanthines are potent synergists of other pesticides known to activate adenylate cyclase in insects. These data suggest that methylxanthines may function as natural insecticides and that phosphodiesterase inhibitors, alone or in combination with other compounds, may be useful in insect control.