Peritoneal mast cells collected from Wistar rats were pooled and purified by differential centrifugation in Ficoll. They were suspended at approximately 10(6) cells/ml in a buffered salt solution, divided into 300 microliters aliquots and incubated at 37 degrees C with or without copper (CuSO45H2O). Histamine release was induced by compound 48/80 or concanavalin-A and estimated from the supernatant following extraction and by fluorimetric techniques. These techniques completely eliminated copper from the final extract. Copper produced a dose-dependent inhibition of histamine release induced by the two agents. The inhibitory effect was present even in cells incubated with copper but washed free of copper before their challenge with the inducing agent. The presence of 10 mM EDTA in the incubating medium almost completely abolished the effect of copper but glucose concentrations up to 25 mM failed to reverse the action of copper.