1'-[4-[1-(4-Fluorophenyl)-1H-indol-3-yl]-1-butyl]spiro[isobenzofuran-1(3H),4'-piperidine] (Lu 28-179) or Siramesine is a sigma-ligand with high specificity for sigma(2)-sites, has been tritiated to directly label these sites in brain. [(3)H]Lu 28-179 bound in a saturable manner to homogenates prepared from rat brain or human cortices with high affinity (K(d)=2.2 and 1.1 nM, respectively) and moderate capacity (B(max)=50+/-12 and 26+/-3 fmol mg tissue(-1), respectively). The rank order of affinity for [(3)H]Lu 28-179 binding to homogenates from human and rat brain was: Lu 28-179>ifenprodil=haloperidol>1,3-di(2-tolyl)-guanidine (DTG)>(-)pentazocinez.Gt;(+)pentazocine. Using in vitro receptor autoradiography to rat brain sections [(3)H]Lu 28-179 binding was shown to be most predominant in the cerebral cortex, piriform cortex, hippocampal formation (CA1-CA3 and dentate gyrus), superior colliculus, molecular layer of the cerebellar cortex and locus coeruleus. Overall, these data are consistent with [(3)H]Lu 28-179 labelling a sigma(2)-like binding site.