Pantethine, a stable disulfide precursor of pantetheine, has been reported to increase intracellular concentration of cysteamine in cultured fibroblasts of patients with cystinosis. In order to determine whether pantethine acts like cysteamine in bringing about depletion of immunoreactive somatostatin (IRS) in rat neural and gastrointestinal tissues and depletion of immunoreactive PRL (IRPRL) in the anterior pituitary, groups of male rats were given pantethine by ip injection at a dose of 0.264 mM or 0.528 mM/100 g body weight or normal saline and killed 4 h later. The interval chosen corresponds to the time of maximum effect after oral cysteamine administration. In cerebral cortex, hypothalamus, duodenal and gastric mucosa, and pancreas, IRS was uniformly depressed by 50% or more as compared with control rats, the most striking changes occurring in the hypothalamus where there was a 64% depletion at the higher dose of drug. Both dosage levels depleted IRPRL in pituitary and serum. At the higher dose, IRPRL was reduced by approximately 85% in the pituitary and 75% in the serum. These findings support the hypothesis that pantethine administration leads to an accumulation of cysteamine within cells throughout the body and that the cysteamine so formed depletes IRS and IRPRL.