Naloxone binding to T lymphocytes seems to occur both at the outer cell surface and in the interior of the cell. The binding sites on the outer membrane appear from previous work to be of low affinity and to be displaced by morphine only at very high concentrations. Permeable cells seem to express both high and low affinity binding sites in their interiors. Morphine readily displaces naloxone from this high affinity site, suggesting that this site may be the long sought after morphine receptor responsible for morphine's naloxone reversible actions on the human T lymphocyte. Do these results suggest that the opiates need to enter the lymphocyte before finding a receptive binding site to initiate their biological activities? Not necessarily. In isolating the lymphocytes, the surface opiate binding sites may be lost because of the exhaustive washing procedures needed for cell purification. The internal receptors may just represent new receptors on their way to the cell surface or used receptors remaining after endocytosis. Or they may indeed represent the true site of action of the opiates on the lymphocyte. Fractionation experiments are currently underway to distinguish between these possibilities.