The blood-brain permeabilities of L-[3H]tyrosine and the tyrosine hydroxylase (TH) inhibitor alpha-[14C]methyl-para-tyrosine ([14C]AMPT) were determined in rat striatum, a brain region rich in TH activity, and in other brain regions containing relatively little TH activity. In striatum, the unidirectional clearance rate (K1) for L-[3H]tyrosine (6.2 ml hg-1 min-1) was significantly greater than the rates for L-[14C]AMPT (2.8 ml hg-1 min-1) and D-[14C]AMPT (0.8 ml hg-1 min-1). The apparent volume of distribution (Vf) for L-[14C]AMPT in striatum (72.5 +/- 4.0 ml hg-1) did not differ from the Vf in other brain regions. The homogeneous distribution of L-[14C]AMPT in rat brain indicates that labeled AMPT is unsuitable for the study of TH in vivo by quantitative autoradiography.