Phosphoinositide hydrolysis was studied in slices of rat striatum and frontal cortex which had been incubated with [(3)H]inositol to prelabel the inositol phospholipids. Dopamine (100 ?M to 10 mM) increased phosphoinositide hydrolysis to a maximum of about 200% compared to control in both areas. Noradrenaline (1 ?M to 1 mM) stimulated [(3)H]inositol phosphate formation to about 400% of control. Dopamine-stimulated phosphoinositide hydrolysis was completely blocked by prazosin; while spiperone and SCH 23390 were partial inhibitors. The ability of noradrenaline (5 to 100 ?M) to stimulate phosphoinositide hydrolysis was antagonized by co-incubation with dopamine (1-10 mM). Low concentrations of dopamine (10 nM and 1 ?M) did not affect total [(3)H]inositol phosphate formation, and ion exchange chromatography of the [(3)H]inositol phosphates failed to show any inhibitory effects on the individual fractions (mono-, bis- and tris-phosphates). Ten mM dopamine, on the other hand, increased the production of [(3)H]inositol mono- and bis-phosphates compared to control. It was concluded that dopamine acts as partial ?(1)-agonist in both the rat striatum and frontal cortex. As such, it increased phosphatidylinositol hydrolysis. Dopamine partially inhibited noradrenaline-stimulated phosphatidylinositol hydrolysis, but it did not inhibit basal rates of phosphatidylinositol hydrolysis.