In order to explore the characteristics of l-stepholidine (SPD) activating the postsynaptic D(1) receptors, the effects of SPD on DARPP-32 phosphorylation in vivo with back-phosphorylation assay and on the postsynaptic D(1) receptor densities with radioligand assay were observed in the striatum of 6-OHDA-lesioned rat. The results showed that following subcutaneously administration of 20 or 40 mg/kg SPD for 21 d, (32)P phosphate incorporation into the DARPP-32 protein in the denervated striatum showed a 50% reduction (P<0.01) vs the intact striatum, indicating an increase of DARPP-32 phosphorylation in vivo in the denervated striatum. However,the D(1) receptor B(max) was decreased from 385.0+/-26.1 to 319.7+/-20.1 fmol/mg protein. It is suggested that D(1) agonist action of SPD decreases the D(1) receptor density but increases the phosphorylation of DARPP-32 in the striatum of 6-OHDA-lesioned rat, which may be responsible for the regulation of D(1) receptor signal transduction in brain neurons.