The effects of MIF-1, its analog cyclo(Leu-Gly) (cLG), and Tyr-MIF-1 on ('3)H-apomorphine binding to striatal D(,2) and D(,3) dopaminergic binding sites were investigated. When tested in vitro, at concentrations ranging from 10('-14) to 10('-3) M, the peptides either had no effect on specific binding or inhibited binding with an IC(,50) greater than 10('-4) M. In an in vivo experiment, injections of MIF-1 (2 mg/kg, SC, once on each of three days prior to assay) and cLG (8 mg/kg, SC, once four days prior to assay) significantly increased the number and decreased the affinity of the D(,2) sites. Both peptides significantly decreased the number of D(,3) sites, but had no significant effect on their affinity. The results of this experiment suggest that MIF-1 and cLG produce their behavioral and physiological effects by altering the number of D(,2) and D(,3) dopaminergic binding sites in the brain