The effect of ionic zinc on the binding of 125I-insulin to a variety of tissues with well-characterized insulin receptors has been assessed. In the isolated rat adipocyte, zinc (250 to 1000 microM) showed dose-dependent stimulation of insulin specific binding, with little change in non-specific binding. This effect was rapid and sustained during a 60 min incubation and was due to a Zn-mediated increase in the number of available binding sites. No changes in binding affinity were apparent. A similar but smaller stimulation of insulin binding was observed at lower Zn concentrations (25-50 microM) in rat liver membranes. In this tissue, higher doses of Zn caused a marked rise in non-specific binding and resulted in the loss of any apparent specific binding of insulin. Similar effects were seen in IM-9 lymphocytes and human placental membranes, although in this latter case the Zn effect on non-specific binding was less marked. These data indicate that ionic zinc exerts a tissue-specific stimulation of insulin binding to its receptors. An intriguing corollary, that requires further study, is that this effect may be related to the known association of insulin with Zn, and thus to an enhancement of insulin action in vivo, at least on the adipocyte.