In vitro receptor autoradiography was used to localize sigma 1 receptors, sigma 2 receptors, and novel haloperidol/DTG-inaccessible sites for sigma and opiate ligands in rat spleen. Sigma-1 receptors were present throughout the spleen, but were most concentrated in the T cell zones. Binding under "sigma 2 receptor-selective' conditions was 70% nonspecific, and sigma 2 receptors could not be detected. Haloperidol/DTG-inaccessible sites had a coarse, punctate distribution in the red pulp and marginal zones of the white pulp. This anatomical localization suggests types of cells and functions that should be examined for modulation by sigma receptors.